Rain Enhancement Technologies Holdco, Inc.

Greetings and welcome to the RAIN Oncology Fourth Quarter and Full Year 2022 Earnings Score. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Dan Ferry of LifeSci Advisors. Thank you. You may begin.

Thank you, operator, and good afternoon, everyone. With me today on the phone are Avinash Phalanke, Chief Executive Officer of RAINN Oncology, Robert Doble, Chief Scientific Officer, Richard Brice, Chief Medical Officer, and Nelson Kabatuan, SVP of Finance. During today's call, Avinash will provide an update on the broader strategic vision for the Mila Demetan franchise. Bob will review the biology and rationale of P53 reactivation as it relates to our Mila Demetan clinical program. Richard will provide an update on RAIN's clinical strategy. 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 involves 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 annual report on Form 10-K for the year ended December 31, 2022, filed with the Securities and Exchange Commission and other SEC filings. All forward-looking statements made during this conference call are based on management's assumptions and estimates as of today, March 9, 2023. 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 Avanish Vlanki, CEO of Rain Oncology. Avanish?

Thank you, Dan. And thanks to everyone for joining us for our fourth quarter and full year 2022 earnings highlights and corporate update. To kick things off, we'd like to remind everyone of our name change to Rain Oncology in late 2022 to mark our anticipated growth as a dedicated and focused precision oncology business. We believe our new corporate name, that reflects who we are and who we intend to remain. As RAIN continues to drive forward with our late-stage clinical program, milodimetan, or MILA, our oral small molecule inhibitor of the MDM2 P53 complex, we'd like to approach today's call by providing context around our goal of demonstrating how P53 reactivation through MILA's disruption of the complex could potentially be transformative in treating a broad range of cancer patients. In the spirit of this, we anticipate the readout from our mantra study to potentially serve as the first validation of p53 reactivation in a phase three clinical setting. If the mantra top line data are favorable, we believe it will signify that reactivation of p53 matters. This will be an important validation as we begin to think about our initiatives beyond de-differentiated liposarcoma or DDLPS. On today's call, we'll also provide highlights from our 2022 progress and achievements. As a bit of biology review, we all know that P53 is the good guy in this story. We want active P53 to do what it's supposed to be doing, which is to protect us from cancer. Today, there are no approved therapies in the treatment of cancer that are aimed at restoring or reactivating this innate anti-cancer agent. Cancer, broadly speaking, needs to find a way to get rid of P53. We all know that mutations in P53 Those instances when P53 is broken and can't bind DNA to allow P53 to do what it's supposed to do occurs in approximately half of all cancers. In the other half, where P53 itself is not broken, cancer has to find other ways to get rid of it. MDM2 is a critical means of deactivating P53 in instances when there are no P53 mutations present. Therefore, in tumors that rely on MDM2 to rid cells of P53, impeding the interaction of MDM2 and P53 could be a route to restoring P53's innate protective properties. And even if MDM2 is not overexpressed, further reactivation or enhancement of wild-type P53 levels might further enhance antitumor activity of target therapies to address other oncogenic drivers. There are a multitude of potential indications to be considered, especially if the tolerability profile of MILA enables a wide-ranging set of combination partners. We believe a positive outcome in the monitor study would legitimize p53 reactivation as a route to treat a range of p53 wild-type cancers. And in that scenario, milodimetan could be the first inhibitor of the MDM2 p53 complex to be submitted and possibly approved by the FDA and other regulatory authorities around the world. Bob will provide additional color on the P53 reactivation story, along with insights from the recent publication in the Journal of Clinical Oncology, before Richard discusses how those data support the novel dose regimen of milodimetan, which is optimized to reduce toxicities associated with MDM2 P53 inhibition. Our clinical strategy, while starting in DDLPS, based on the totality of the data present at the time of licensing the program in 2020, will aggressively move to larger patient populations based on the experience we have gained with Mila in the clinic. We point out that after our initial indication in DDLPS targeting approximately 1,400 patients per year in the U.S., our subsequent studies in the Mantra 2 basket study targets 8,000 patients per year in the U.S., and our third planned study, the Mantra 4 study, will target over 40,000 patients per year domestically. That pattern should convey how we approach creating value for the MILA franchise, and as we evaluate the potential of both monotherapy and combination opportunities across the approximately 50% of the cancer population possessing wild-type p53 tumors. I'll ask Bob and Richard to talk in more detail around recent data presented and the clinical strategy for meledimetan. I do want to comment briefly, however, on our preclinical research program focused on developing an inhibitor of RAD52, We have made a strategic determination to terminate this program. Based on data we have generated for the RAD52 research effort, we do not anticipate a meaningful probability of success. Therefore, we are electing to focus our resources on identifying new indications for milodimetan or additional precision oncology programs by external licensing or internal development that may represent a more efficient deployment of capital for rank. In the prior quarter, we also remind you that we further improved our cash position with a $50 million registered offering concurrent with the release of the early Mantra 2 data. We're excited to welcome several new large healthcare-focused funds to RAINN as part of that financing. Our year-end cash position of approximately $130 million provides a runway to complete all current, ongoing, and planned clinical trials of Melodematam. This includes the Phase 3 Mantra trial in DDLPS for which data is expected in the second quarter of this year. It includes the ongoing Phase II Mantra II basket trial and the planned Phase I-II Mantra IV basket trial, which we expect to commence by midyear. With that, I'd like to turn it over to our President and Chief Scientific Officer, Dr. Bob Doble.