Rain Enhancement Technologies Holdco, Inc.

Good day, and welcome to the RAIN Therapeutics Second Quarter 2022 Earnings Conference Call. Today's conference is being recorded. At this time, I'd like to turn the conference over to Bob Yeti. Please go ahead.

Thank you, Operator, and good afternoon, everyone. With me today on the call are Avinash Balanki, Chief Executive Officer of RAIN Therapeutics, Nelson Kabat-Juan, SVP of Finance. During today's call, Avanesh will provide an overall business update, including RAINN's clinical programs and 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 RAINN's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results may differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, as described in RAINN's annual report on Form 10-K for the year ended December 31, 2021, and subsequent filings with the Securities and Exchange Commission. All forward-looking statements made during this conference call are based on management's assumptions and estimates as of today, August 4th, 2022. 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 said, it's my pleasure to turn the call over to Avinash Belanki. CEO of Varian Therapeutics. Abhinish.

Thank you, Bob. And thanks to everyone for joining us for our second quarter earnings call. We are pleased to share updates today on our two ongoing clinical trials, the Mantra Phase 3 Registrational Trial in patients with liposarcoma and the Mantra 2 Tumor Agnostic Basket Trial in advanced solid tumor patients exhibiting MDM2 gene amplification. We're going to have a different format on this call with prepared remarks from myself and Nelson Kabatouan, Reign Senior Vice President of Finance, and then move more quickly to Q&A, where we'll be joined by our President and Chief Scientific Officer, Dr. Bob Doble, and our Chief Medical Officer, Dr. Richard Bryce. First and foremost, we announced earlier this morning that we had completed enrollment in the Phase III MONTRA trial in patients with well-differentiated, de-differentiated liposarcoma. As of the end of July, we completed enrollment with 175 patients, exceeding our 160 patient target, and five months ahead of our prior year-end guidance. We saw a clear acceleration of enrollment since our update call at the end of the first quarter of this year, at which point we announced we were approximately half enrolled. We believe this speaks to the tremendous unmet need in patients with de-differentiated liposarcoma, for which milidimetan offers a targeted therapeutic strategy relative to standard cytotoxic options. We enrolled across 70 international sites in the U.S., Europe, and Asia. As a reminder, this pivotal trial compares milidimetan monotherapy to the approved agent yondelus or trebectodine. Melodematin was dosed at 260 milligrams daily for three days, followed by 11 days off therapy. We refer to this as the three out of 14 day schedule. We anticipate top line data from this trial in the first half of 2023. We also anticipate that if the mantra data are supportive, we would submit an NDA for melodematin and liposarcoma in the U.S. with similar submissions in Europe and possibly other regions as well. Second, our Phase II tumor-agnostic MONTRA-2 trial is progressing as planned, with 11 sites activated in the U.S. to date and additional just-in-time sites opening as necessary from referrals from the TEMPEST and CARIS genomic testing services. To recap, this trial is evaluating milidimetan in multiple solid tumor types in patients with P53 wild-type tumors that exhibit high MDM2 gene amplification at a copy number of 12 or greater. We anticipate enrolling approximately 65 patients across a range of solid tumors and using the same dosing regimen as in the registration mantra trial and continue to anticipate interim data of the first 10 valuable patients in the fourth quarter of this year. We continue to anticipate commencing two additional trials before year end. both the MONTRA-3 trial in Merkel cell carcinoma and the MONTRA-4 trial evaluating the combination of milidimetan with a checkpoint inhibitor, which is a tezolizumab, in patients with p53 wild-type advanced solid tumors that exhibit loss of the gene CDKN2A. Also, at the recent annual ASCO meeting, we presented preclinical data detailing the rationale for the MONTRA-4 trial. New preclinical data across multiple in vivo tumor models with CDK N2A loss and wild type P53 supported potential synergy of milodimetan and an immune checkpoint inhibitor in this genetic subset. We remain very excited about the potential for the MONTRA4 trial and its strategy. With that, I'd like to turn it over to Nelson to review our financial results. Nelson?

Thank you, Avanish, and good afternoon, everyone. I am pleased to provide an update to our financial results for the second quarter ended June 30th, 2022. I would also like to invite you to review our form 10-2 filed today for more details. For the second quarter of 2022, we reported a net loss of 17.6 million compared to net loss of 8.2 million in the second quarter of 2021. Research and development expenses were 14.3 million in the second quarter of 2022, as compared to $5.5 million in the second quarter of 2021. The increase was primarily driven by R&D costs, mainly for our lead candidate, Mila Demetan, from the ongoing Phase 3 Mantra clinical trial or ongoing Phase 2 Mantra 2 trial, as well as personal costs. As of June 30, 2022, RAINN continues to have a strong balance sheet with $106 million in cash, cash equivalents, and short-term investments. We anticipate that our second quarter cash position will provide runaway into mid-2024, and we believe that the Melodemotan program is well-funded. With that, I'm going to turn the call back over to Avnish.

Thanks, Nelson. RAIN continues to focus on the clinical execution of our Melodemotan program, and we're thrilled with the rate of progress thus far, particularly with enrollment now completed in our Registrational Phase III Montra trial five months earlier than previously guided. Rain anticipates a broad clinical data set for Melodemetin with a steady cadence of updates over the next two plus years. We look forward to phase three monitor data in the first half of 2023. With that, we'll have Dr. Bob Doble and Dr. Richard Bryce join us and available to answer questions. Operator?

Thank you, if you'd like to ask a question, please signal by pressing star one on your telephone keypad. If you're using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, let's press star one to ask a question, and we'll pause for a moment to allow everyone an opportunity to signal. We'll take our first question from the line of Michael Smith with Guggenheim.

Oh hey, good afternoon. This is Ige Ahn for Michael. Thanks for taking our questions and congrats on the earlier than expected enrollment for MnDRAC. I guess we'll start with a question on LPS. So one competitor has presented some early data at ASCO, you know, on its MDM2 inhibitor in LPS. So what do you think of the potential read-through from the, you know, from the presented data to Melodermatin's competitive positioning into the ongoing management study? And I have a follow-up. Thank you.

Hi, Yuge. This is Avadish. Thanks for the question. Let me turn the question over to Bob.

Thanks for the question, Yuge. Of course, we're not going to comment on that. However, we have read that BI's entry into the MDM2 space validates our approach at RAIN using MDM2 as a validated cancer target in select patient populations.

Got it. And then, I guess as a follow-up, can you elaborate your current thinking and, you know, consideration around the first-line strategy? in LPS either with monotherapy or maybe perhaps even in combination with other agents.

Thanks. Yeah, I'm happy to take that one, Yige. So obviously we want to wait on mantra results before starting to articulate subsequent plans. So I think that's first and foremost, but I think we will comment that If successful, if Mantra does have a successful outcome, our expectation would be to expand the opportunity across a multitude of indications inclusive of frontline liposarcoma. But we don't want to get into the details of what that looks like at this moment in time.

Okay, great. Thank you very much.

Absolutely.

We'll take our next question from the line of Joe Consenzaro with Piper Sandler. Please go ahead. Your line is now open.

Hi, this is Sam on for Joe. Thanks for taking our question. Could you just provide a little more detail on what you think drove this acceleration in enrollment? And then now with this rapid acceleration, do you think that the top line data can now come maybe in the early part of first half 23?

Hi, Sam. Thanks for the question. Let me turn that over to Richard.

Sure. Happy times for that. So I think this speaks to two things. First of all, I do want to take this opportunity to call out the excellence of our clinical team and our collaborative partners with this achievement, this incredible enrollment into the study in the last six months. I think that surpassed expectations both at our level and at the physician level. What does it mean? Beyond that, I think it's important that it underlines or underscores the tremendous enthusiasm amongst physicians and patients for a new treatment option, particularly a targeted treatment option for patients with DNF liposarcoma, which as we know is MDM2 amplified by definition. And so that's really reflected in the enormous enthusiasm to enroll into the study, and we would expect to see that play itself out in future trials and in future circumstances, hopefully if the study is positive in the commercial setting as well.

Great, thank you.

We'll take our next question from the line of Jeff Jones with Oppenheimer. Please go ahead. Your line is now open.

Thank you and good afternoon, guys. I guess two questions from me. On the MONTRE2 basket trial, any idea what kind of duration response data you'll have in hand when that reads out top line end of the year? And then the second question, any update on the RAD52 program?

Hi, Jeff. Thanks for the question. Let me turn that question over to Bob.

Yeah, so to answer the first part of the question regarding Mantra 2, we've messaged in the past that we expect to have 10 patients with a meaningful operational follow-up. This would be at least four months or approximately two scans for those patients as the minimum duration, and that expectation has not changed. Regarding your second question on the RAD52 program, we are continuing to progress that project, and we've signaled in the past, however, that we have mitigated spend on that to focus on milidimetan, and based on that,

which will progress in the RAD52 program. Great. Thanks.

Once again, if you'd like to ask a question, that's press star 1. And we'll take our next question from Sumit Roy with Jones Research. Please go ahead. Your line is now open.

Hi, everyone. Possibly this is a question for Bob. I was wondering, as we are seeing in multiple phase three trials, the standard of care or the control arm is outperforming the historical data. Anything that possibly due to better tumor monitoring or better supportive care? So I'm curious to get your thoughts on if you think the control arm could outperform the seven-year or eight-year-old historic data or if there is any concern for that.

Thanks for the question, Shomit. Bob?

Yeah, no, you know, I think this is, we're looking at data, obviously, from the registrational trial of Travectin, which is the clinical arm in our trial. That is a modern clinical trial with robust subset analysis, and we see no indication to expect that Travectin will outperform in the mantra study compared to its registrational data.

Let me add there's some of that, of course, to predict, but as a reminder in terms of the clinical trial design for Mantra, we actually did assume that the control arm would modestly be improved from its efficacy from the registrational study. So we did actually anticipate any potential improvement. We still anticipate an opportunity to succeed for indemnity.

Great. I have a quick second question, if I may. Are you allowing crossover from the control arm in the trial, mantra trial?

No, we're not. We're not. There's no crossover in mantra.

All right. Thank you so much for taking the questions. And congratulations on the fast enrollment.

Thank you so much.

We'll take our last question from the line of Tony Butler with Roth Capital. Please go ahead. Your line is now open.

Yes. Thanks very much. I just wanted to ask about Mantra 4 since it's one of the things we haven't discussed this evening in detail given the population size and the opportunity for the compound in that CDK in 2A population. And as you're Looking forward to that trial, I would think that the number of sites that could or would like to participate would be quite a few. Could you just provide a brief discussion, if I may, on are you thinking about a small number or would you get in with both feet and perhaps expand it, including internationally? Thank you. Even if it is a phase one, I understand.

Thanks for the question, Tony. Let me turn the question over to Bob.

Yeah, thanks for the question. You know, obviously the MONTRA-4 study is very similar to the MONTRA-2 study, which is ongoing in the fact that it is a basket design, all cumbersolid tumors, genetically selected patients. So we hope to take the learnings from the MONTRA-2 trial into the MONTRA-4. You can expect probably some overlap in terms of the sites that we've used. Obviously, as you mentioned, the population is far larger for the CDK into a loss population. And therefore, we would expect enrollment, you know, on a kind of per site basis to be much, much faster given the population of those. So hopefully that answers your question.

Thank you, Bob. Appreciate it.

That concludes today's question and answer session. I'd like to turn the conference back over to Mr. Valenka for any additional closing remarks.

Thank you, Operator, and we want to thank everyone for joining us on this quarter's earnings call, and we look forward to updating everyone on our progress over the next quarter. Thank you.

This concludes today's call. Thank you for your participation. You may now disconnect.