Rain Enhancement Technologies Holdco, Inc.

Good afternoon and welcome to the RAIN Therapeutics second quarter 2021 financial results and highlights of recent progress conference call. My name is Reese and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. During the question and answer session, if you have a question, please press star then one on your touchtone phone. I will now turn the call over to Glenn Garman With Lifestyle Advisors, Glenn, you may begin.

Senior Vice President of Finance. During today's call, Avinash will provide an overall business update. Richard will provide an update on RAINN's clinical programs. Bob will provide an update on research efforts, and Nelson will review the financials. Before we begin, I'd like to remind you that statements made during this conference call that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based upon RAIN's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties as described in RAINN's quarterly report on Form 10-Q for the quarter ended March 31st, 2021 and subsequent filings with the SEC. All forward-looking statements made during this conference call are based on management's assumptions and estimates as of today, August 10th. RAINN undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after today except as required by law. With that, I'd like to turn the call over to Avinash Vallaki, CEO of RAIN Therapeutics. Avinash.

Thanks, Glenn. And thanks to everyone for joining us for our first earnings call as a public company post our initial public offering this past April. As our first call, we'll be a bit more comprehensive about the overall clinical development strategy for our lead program, our MDM2 inhibitor called meledimetan, also known as RAIN32. We may refer to meledimetan as Milla for short. In this most recent quarter, we worked towards putting our vision for milodimetan in action. We continue to view our program as a potential best-in-class MDM2 inhibitor. We're excited about the therapeutic window afforded by Mila because we believe it lends an opportunity to pursue almost 50% of all cancers. As a reminder, MDM2 inhibition is a strategy to reactivate p53, called the guardian of the genome, and MDM2 acts as a mechanism for cancer cells to circumvent the protective properties of p53. Now, p53 is mutated in approximately half of all cancers and therefore largely loses its relationship to MDM2 in those settings. So we do not expect MDM2 inhibition to be a relevant strategy in the half of cancers with mutated p53. However, the other 50% of cancers are cancers with wild-type p53 and where p53 might be inactivated by MDM2. We believe inhibiting MDM2 could be effective there. Our clinical strategy for MILA will be a one-two punch and focused on the wild type P53 population. Step one will be to pursue clinical indications where we have confidence of tumor dependence on MDM2. The first three clinical trials that we have previously articulated and we'll review again shortly are all MDM2 amplified P53 wild type cancers. All our clinical discussion today will be in this category. However, it's also possible to be MDM2-dependent without MDM2 gene amplification, and we're doing more work there. We hope to present non-clinical support for MILA and those additional tumor types to support further investigation. Therefore, MDM2-dependent cancers, either through gene amp or other routes, is step one of our clinical strategy and where we expect there to be the most sensitive patient population to MDM2 inhibition. Step two of this one-two punch will be in other p53 wild type tumors. In the second step, single agent MDM2 inhibition is not likely to be sufficient on its own and will require a combination with other agents. An example of this are indications like acute myeloid leukemia. We've seen many large biopharmas with MDM2 inhibitor programs historically jump straight into AML because of the patient opportunity. Although we do not believe AML to be an MDM2 dependent cancer, It is, however, predominantly P53 wild type. As such, MDM2 inhibition and AML will likely need synergistic combination agents. These other wild type P53 indications will be step two of our plan, and we think a well-tolerated MDM2 inhibitor program that is combinable with other agents can hold great promise. Today's call will largely be focused on step one, focusing on those patients we expect to be most sensitive to MDM2 inhibition. Let me share what we've been up to. In the second quarter of this year, we work towards getting a pivotal phase three trial started in patients with certain subtypes of liposarcoma, or LPS. The first trial being planned for Mila is in LPS patients with a histology type called D-differentiated liposarcoma, or DD-LPS for short. Patients with DD-LPS are eligible for the study with or without the presence of a related subtype called well-differentiated LPS, or WD-LPS. These two subtypes most often coexist. The reason for pursuing these two subtypes of LPSs is that, again, all patients with these subtypes exhibit MDM2 gene amplification. And because all patients have this gene amp, we don't need a companion diagnostic for this patient population. Post the second quarter in July, we've already announced that the phase three trial, now dubbed the MANTRA study, has now started, the first patient having been randomized. With Mantra now started, we expect to commence our second clinical study, a phase two tumor agnostic basket study in patients with advanced solid tumors in the second half of 2021. And that will be called the Mantra 2 study. These patients will be prospectively selected based on a certain threshold of MDM2 gene amplification. For Mantra 2, we will need a companion diagnostic strategy in the future as it's a biomarker selected population. We plan to follow that up with a second study with the third trial and another phase two trial in patients with intimal sarcoma. And that study is anticipated to commence by early 2022. Intimal sarcoma, Likert strategy, and liposarcoma is another largely MDM2 gene amplified tumor type, and therefore no companion diagnostic strategy needed here either. Again, all three studies are in patients with MDM2 gene amplification. We continue to anticipate data timelines in line with what we stated in our recent S1 filing. The very first data read from our Melodematam program is anticipated to come from Mantra 2, the phase two tumor agnostic basket trial, with interim data in the second half of 2022. The second set of data is expected to come as interim data from the phase two study in intimal sarcoma in late 2022. And then third, top line final data from the pivotal antra study in DDLPS in 2023. Therefore, we anticipate a steady stream of clinical news flow beginning in the second half of next year. Finally, we are very excited about working on a potential first-in-class strategy for DNA repair with our RAD52 research program. RAD52 inhibition is a strategy to address the limited therapeutic options in the DNA repair space, and especially the need in patients after relapse from PARP inhibitors. The program is early, and we continue to expect selection of a lead candidate in 2022. We look forward to telling you more about our progress with this program when we can. With that, I'll turn it over to our chief medical officer, Dr. Richard Bryce.