Rain Enhancement Technologies Holdco, Inc.

And additional just-in-time sites will be opened as necessary from referrals from the Tempus and Carus Genomic Testing Services. We anticipate enrolling 65 patients across a range of solid tumors and using the same treatment protocol as in the Registrational Mantra Trial. That is with melidometan dosed at 260 milligrams in the three out of 14-day schedule. We anticipate an early data readout in the fourth quarter of this year and reporting patient responses, duration of response, and safety in approximately 10 evaluable patients. Based on the progress made with our Milodermatan clinical program thus far, we're looking forward to commencing two additional studies in the fourth quarter of this year. As Avinash mentioned, we anticipate starting the Mantra 3 study of Milodermatan in patients with Merkel cell carcinoma who are resistant or refractory to checkpoint inhibitor therapy. As a reminder, we believe the majority of patients with Merkel cell carcinoma, up to 80% of them, have a cancer induced by the polyomavirus, which induces MDM2 overexpression. We are also encouraged by data from other MDM2 inhibitor programs revealing monotherapy activity in the tumor setting. and hence believe that there is an opportunity for an MDM2 inhibitor program that may be better able to manage the on-target cytopenic toxicities. And finally, we're excitedly anticipating the initiation of our fourth study before year-end to evaluate our first combination regimen with milidimetan. This study, the Mantra 4 study, will evaluate the combination of milidimetan and rocistocentric, or atezolizumab. in a phase 1-2 study in approximately 30 patients with wild-type P53 advanced solid tumors that also exhibit loss of the CDKN2A gene. As a reminder, we believe loss of the gene CDKN2A and loss of its protein product, P14R, leads to increased MDM2 levels. P14R is a natural regulator of MDM2. There are a significant number of patients with wild-type p53 solid tumors with advanced disease that exhibit loss of CDKN2A. This is estimated at over 35,000 patients per year in the U.S., as many as 6% to 7% or more of all solid tumors, and is the second most common tumor suppressor aberration after p53 mutations. The Mantra 4 study will be primarily focused on confirming the safety of the combination regimen but we'll also evaluate efficacy. With multiple clinical strategies for Melodermatin underway, we're excited for all the potential new data. So let me turn now over to our Chief Scientific Officer, Bob Doble. Bob.

Thanks, Richard, and good afternoon, everyone. First, RAINN recently presented additional data relating to the Montreux 2 patient population at the AACR annual meeting in New Orleans. This work further detailed the variety of tumors that harbor high-level MDM2 gene amplification using RAIN's copy number threshold of 12 and showed a meaningful number of patients with lung, breast, bladder, and gastroesophageal tumors, amongst others. Although CDK4 is commonly co-amplified with MDM2 in dedifferentiated liposarcoma and other sarcoma subtypes due to its proximity on chromosome 12, This presented work demonstrated a notable lack of CDK4 co-amplification in lung, breast, bladder, and gastroesophageal tumors, amongst others, particularly at the copy number 12 threshold. Although the impact of oncogenic drivers remains unknown with respect to clinical benefit of MDM2 inhibition, this analysis only found approximately 20% of patients with MDM2 amplification and a known oncogenic driver mutation. Analysis of TCGA data demonstrated a worse overall survival for patients whose tumors have MDM2 copy number 12 or greater with wild-type TP53, highlighting the unmet need in this patient population. We presented a population analysis of over 50,000 patients with solid tumors across the AACR Genie and TCGA databases. which confirmed the presence of MDM2 copy number 12 or greater with wild-type TP53 in 1.2% of all cancer patients. Second, Dr. DiCaprio's group at Dana-Farber presented preclinical data last month at the Second International Symposium of Merkel cell carcinoma, demonstrating robust activity of niladiametanin in in vivo PDX models of Merkel cell. This preclinical data supports our upcoming Mantra 3 study. Third, RAINN will present an abstract of the upcoming ASCO annual meeting in Chicago relating to the patient population eligible for the upcoming Mantra 4 clinical study. In addition to tumor-specific frequencies of CDKN2A loss in the setting of wild-type TP53, RAINN plans to present new data supporting the rationale behind our first combination trial of noledatatin and atezolizumab. Finally, we remain excited about RAD 52 as a synthetic lethal target, and internal research efforts at RAINN are ongoing to advance this program. And with that, let me now turn it over to Nelson to review our financial results. Nelson?

Thank you, Bob, and good afternoon, everyone. I'm pleased to provide an update to our financial results for the first quarter ended March 31, 2022. I would also like to invite you to review our Form 10-Q file today for more details. For the first quarter of 2022, we reported a net loss of $17.4 million compared to a net loss of $6.8 million in the first quarter of 2021. Research and development expenses were $13.6 million in the first quarter of 2022 as compared to $5.3 million in the first quarter of 2021. The increase was primarily driven by R&D costs, mainly for our lead candidate, melidematin, from the ongoing Phase II Mantra clinical study, or ongoing Phase II Mantra II study, as well as personal costs. General and administrative expenses were $3.9 million for the first quarter of 2022, compared to $1.5 million for the first quarter of 2021. The increase was primarily driven by higher third-party G&A costs, including personnel, insurance, legal, accounting and audit, and outside consulting fees. As of March 31, 2022, RAINN had $123.2 million in cash, cash equivalents, and short-term investments. And we anticipate that our 2022 year-end cash position will provide runway in the first half of 2024. We expect our Melodematon clinical program to be well-funded. With that, I'll now turn the call back to Avinash.