Q3 2021 Rain Therapeutics Inc Earnings Call

November 10, 2021

Speaker 1: Ladies and gentlemen, thank you for standing by. Your conference calls should begin momentarily.

Ladies and gentlemen, thank you for standing by your conference call will begin momentarily again, thank you standing by.

The conference concept of getting on mechanics.

[music].

Speaker 2: ["Pomp and Circumstance"] ["Pomp and Circumstance"]

Okay.

Speaker 1: Thank you for standing by and welcome to the RAIN Therapeutics third quarter 2021 Financial Results Conference call. At this time all participants on a listen only month.

Thank you for standing by and welcome to the rain Therapeutics third quarter 2021 financial results conference call at this time, all participants on a listen only mode.

Speaker 1: After this piece of publication, there will be a question and answer session. To ask a question of that time, please press star then one when you catch shown tele.

After the Speakers' presentation there'll be a question and answer session to ask a question at that time. Please press Star then one when you touch tone telephone.

Speaker 1: As a reminder, today's conference is in recorded. I will now enter the conference to rehearse Mr. Bob Yettich, first, you may begin.

As a reminder, today's conference call is being recorded.

I would now like turn the conference where he held Mr. Bob yet it Sir you may begin.

Yeah.

Thank you operator, and good afternoon, everyone with me today on the phone or on the nature of Milwaukee, Chief Executive Officer, Robert Double Chief Scientific Officer, Richard Bryce Chief Medical Officer.

Speaker 3: Thank you, operator. Good afternoon, everyone. With me today on the phone, I'm Robin H. Philunky. Chief Executive Officer, Robert Dullbell. Chief Scientific Officer, Richard Bright. Chief Medical Officer.

Speaker 3: and Nell Tune Cabo-2 on Team Braisers and End of Finance.

And Nelson covered Chuan senior Vice President of Finance.

Speaker 3: During today's call, Avonage will provide an overall business update, which will provide an update on rent.

During today's call <unk> will provide an overall business update.

Richard will provide an update on <unk> clinical program.

Speaker 3: Bob will provide an update on research efforts and Nelson will review the finance.

Bob will provide an update on our research efforts and Nelson will review the financials.

Speaker 3: Before begin, I'd like to remind you that statements during this conference call that are not historical facts are for the statements within the meeting of the private, curious litigation reform act of 1995.

Before we begin I'd like to remind you that statements. During this conference call that are not historical facts are forward looking statements within the meaning of the private Securities Litigation Reform Act of $19 95.

Speaker 3: These four of the statements are based on RAIN's current expectations and involve assumptions that we never materialize or prove to be correct.

These forward looking statements are based on <unk> current expectations and involve assumptions that may never materialize or prove to be correct.

Speaker 3: actual results could differ materially from those anticipated as such for the statements. As a result of various risks and uncertainties, as described in Reigns quarterly report, informed 10Q for the quarter ended March 31, 2021. And subsequent filings with the Turies and Exchange Commission.

Actual results could differ materially from those anticipated in such forward looking statements as a result of various risks and uncertainties as described in <unk> quarterly report on Form 10-Q for the quarter ended March 31 2021.

Subsequent filings with Securities and Exchange Commission.

Speaker 3: All four of the key statements made during this conference call based on management's assumptions and estimates as of today, do remember 10.

All forward looking statements made during this conference call based on management's assumptions and estimates as of today November 10.

Speaker 3: Rain undertakes nobligation to update such statements to reflect events that may occur or circumstances that exist after today, except is required by law. With that, my pleasure to turn the call over to nomination, Philonky, CEO of Rain. Avonese.

<unk> undertakes no obligation to update such statements to reflect events that occur or circumstances that exist capture today.

As required by law.

With that it's my pleasure to turn the call over to nomination philosophy CEO of ring of a niche.

Speaker 4: Thank you, Bob, and thanks to everyone for joining us for a third quarter earnings call. As a matter of principle for these earnings calls,

Thank you Bob and thanks, everyone for joining us for our third quarter earnings call as a matter of principle for these earnings calls we're going to make it standard practice to be very brief and we'll leave it to the Q&A to address the details that are the most interest in this.

Speaker 4: We're going to make it standard practice to be very brief. And we'll leave it to the Q&A to address the details that are of the most interest. In this most recent quarter and since the end of the third

Most recent quarter and since the end of the third quarter, we continued to advance <unk> and Rad 52 programs forward.

Speaker 4: Rain continues to advance the Mill of Dematine and RAD 52 programs forward. As a reminder, we'll continue to refer to Mill of Dematine as Mila, wherever appropriate.

Minder will continue to refer to <unk> as Miller wherever appropriate first and foremost are phase III trial. The mantra study for <unk> in patients with LIFO sarcoma is proceeding according to plan with sites being activated on a regular basis around the world as a potential registration enabling study there is no interim read.

Speaker 4: First and foremost are phase three trial, the mantra study from Milla and patients with light will sarcoma is proceeding according to plan with fights being activated on a regular basis around the world. As a potential registration enabling study, there is no interim read with final data anticipated in 2023, Richard will provide some more color here.

With final data anticipated in 2023, Richard will provide some more color here.

Speaker 4: Second, we also expected dose of first patient in the phase two tumor agnostic mantra two study shortly, and we'll announce that when it happens. This trial will evaluate Miller and a tumor agnostic signal finding basket study across 65 patients in the US with solid tumors that exhibit a certain threshold of MDM2 gene amplification. We expect to provide an interim update from mantra two in the second half of next year.

We also expect to dose our first patient in the phase two tumor agnostic mantra to study shortly and we will announce that when it happens. This trial will evaluate Milan, a tumor agnostic signal finding basket study across 65 patients in the U S with solid tumors that exhibit a certain threshold of MDM to gene amplification.

We expect to provide interim update for monitoring <unk> in the second half of next year.

Speaker 4: Third, we announced that we will re-prioritize our clinical strategy for our third plan study towards Merkel cell carcinoma, replacing our prior plan study of intemal sarcoma. This new trial will be called mantra three.

Third we announced that we will re prioritize our clinical strategy for third planned study towards Merkel cell carcinoma, replacing our prior planned studies intervals sarcoma. This new trial will be called mantra three.

Speaker 4: The decision to prioritize Merkel cell was made for three key reasons. One, new nonclinical data presented by the Dana Farber Cancer Institute demonstrating compelling efficacy for Milledemotan, which already adds to the biologic rationale that many Merkel cell tumors are MDM3 dependent.

The decision to prioritize Merkel cell was made for three key reasons, one new non clinical data presented by the Dana Farber cancer Institute, demonstrating compelling efficacy for <unk>, which already adds to the biologic rationale that many merkel cell tumors are <unk> dependent.

Speaker 4: We know there's already been presented signs of activity with MDM2 in addition in Merkel cell from other MDM2 inhibitor programs.

Two we note theres already been presented signs of activity with <unk> inhibition in Merkel cell from other MDM chew inhibitor programs.

Speaker 4: And three, the larger addressable market size of Merkle cell as compared to income loss sarcoma, hence representing the most appropriate use of our financial resources.

And three the larger addressable market size of the Merkel cell as compared to income will start coma, hence representing the most appropriate use of our financial resources based on the larger population of Merkel cell faster projected patient accrual rates.

Speaker 4: Based on the larger population of Miracle Cell, faster projected patient accrual rates and an expected shorter trial duration, the new plan Miracle Cell study has no significant impact on range cash one way.

And unexpected shorter trial duration, the new plan Merkel cell study has no significant impact on <unk> cash runway.

Speaker 4: We expect mantra three to enroll 34 patients in the US in the second line or later settings among patients relapsed to checkpoint inhibitors, which is the standard of care in the front line. And we expect to start the study in the middle of 2022.

We expect mantra three did enroll 34 patients in the U S. In the second line or later settings, among amongst patients relapsed to checkpoint inhibitors, which is the standard of care in frontline and we expect to start the study in the middle of 2022.

Speaker 4: Finally, we held an R&D day yesterday, where we host several prominent key opinion readers across various treatment specialties, where we think MDM2 inhibition could be applied.

Finally, we held an R&D day yesterday, we'll be hosting several prominent key opinion leaders across various treatments specialties, where we think <unk> two inhibition could be applied speakers included Dr. <unk> theory from Brown University.

Speaker 4: speakers included Dr. Wafik Al-Diri from Brown University, who many of you may know for his discovery of P21.

Many of you may know for his discovery of $2 21, doctors, Manav grounder and David Hong from Memorial Sloan Kettering, MD Anderson cancer centers, respectively, who will be participating in <unk> first two clinical studies for Miller and.

Speaker 4: Dr. Smernaul Grounder and David Haung from Memorial Sloan Kettering and MD Anderson Cancer Centers, respectively, who will be participating in range first to clinical studies for Mellup.

Speaker 4: and Dr. Gwahanana and James C. Taprio from Dana Farber for their expertise in Mirkelsel Karsinoma. We also included talks from Dr. Francois Clement-Begarde and Sylvia Stachiati, who shed light on some additional clinical opportunities from the lab.

And doctors, Gwen Hana and James could tap real from Dana Farber for their expertise in Merkel cell carcinoma.

Also included talks from doctors Francois comment the guard and Sylvia stack, Yati, who shed light on some additional clinical opportunities for Miller.

Speaker 4: Our strategy continues to be to focus our early effort on the most sensitive MDM to dependent tumor types first, and will be followed by combination strategies to further enhance patient outcomes and other P53 wild type cancer.

Our strategy continues to be to focus our early effort in the most sensitive <unk> dependent tumor types first and will be followed by combination strategies to further enhance patient outcomes and other P. 53, wild type cancers, we're very excited about the potential for a range of opportunities from a kind of a meaningful impact.

Speaker 4: We're very excited about the potential for a range of opportunities from Milla to have a meaningful impact on patient care.

On patient care.

Speaker 4: Blast the early preclinical work around programs targeting RAD 52 continues to move forward and we expect to provide updates at future at future scientific symposia as appropriate.

First the early preclinical work around programs targeting rapid Youtube continues to move forward and we expect to provide updates at future and future scientific symposia as appropriate.

Speaker 4: With that, I'd like to turn it over to our chief medical officer, Dr. Richard Brace.

With that I'd like to turn it over to our Chief Medical Officer, Dr. Richard Bryce.

Speaker 5: Thank you, Evan and good afternoon everyone.

Kevin.

And good afternoon, everyone.

Speaker 5: Following on from our last earnings call in August , where we announced the start to our pivotal phase three mantra study, indeed differentiated like the sarcoma, we are progressing the site activation throughout the US and Europe , anticipating approximately 30 sites to be open by the end of the year, with the remaining 45 sites in Europe , North America, and certain Asia Pacific countries, coming on stream before the end of the first quarter of 2022. Patient enrollment continues.

Following on from our last earnings call. It August where we announced the start trial pivotal phase III <unk> study indeed translated like the sarcoma, we are progressing with site activations throughout the U S. Europe anticipating approximately 30 sites to be opened by the end of the year with the remaining 45 site in Europe.

America, and certain Asia Pacific countries coming on stream before the end of the first quarter 2022.

Patient enrollment continues as expected.

Speaker 5: I am pleased to announce today that our second trial, the Mantra 2 Basket Study, is now active and open to enrollment.

I am pleased to announce today that our second trial. The manager two basket study is now active and open to enrollment we will make a separate announcement when the first patient is dosed.

Speaker 5: We will make a separate announcement when the first patient is those.

Speaker 5: We expected the Manchu-2 study will ultimately be opened in a total of approximately 10 sites throughout the United States with additional just-in-time sites as necessary from the Tempest and Carousel referral.

We expect the demand to two study will ultimately be opens in a total of approximately 10 sites throughout the United States with additional just in time sites as necessary from the templates and carers referrals.

Speaker 5: The study is open to patients that are P53 wild type and MDM2 amplified with a minimum gene copy number of 12 or a six-fold increase in copy number by local testing methods.

The study is open to patients that are P 53, wild type and the MTM to amplified with a minimum gene copy number of 12 or six fold increase in copy number by local testing methods.

Speaker 5: As we previously discussed, this threshold is chosen because the high gene amplification at these levels has been observed to exclude P53 mutations, thereby ensuring MDM2 as the oncogenic driver in these tumors.

As we previously discussed this threshold is chosen because the hygiene amplification that these levels has been observed to exclude P 53 mutations, thereby ensuring M. D M. Two as the oncogenic driver in these tumors.

Speaker 5: As well as the in-house genomic screening at the selected U.S. site, we have partnered with Tempest and Carrus for a follow-up patient's meeting these particular criteria.

As well as the in house genomics screening at the selected U S sites we.

We have partnered with 10% tariffs for <unk>.

<unk> of patients meet her needs particular criteria.

Speaker 5: The study aims to enroll 65 patients across a range of solid tumors. And the treatment protocol is the same as in the Registrational Mantra study.

The study aims to enroll 65 patients across a range of solid tumors.

And the treatment protocol is the same as in the Registrational mantra study.

Speaker 5: That is 260 milligrams orally, once daily for three consecutive days out of 14.

That is 260 milligrams orally once daily for three consecutive days out of 2014.

Speaker 5: And as we previously advised, we anticipate an interim analysis and data readout in the second half of next year.

And as we previously advised we anticipate an interim analysis and data readout in the second half of next year.

Speaker 5: As Avinish mentioned, we have deprioritized our internal sarcoma program to focus on the opportunity in Merkel cell carcinoma in the second line setting. Following a immune checkpoint to stop shot.

Does that have any just mentioned we have deep prioritize our internal sarcoma program to focus on the opportunity in Merkel cell carcinoma in the second line setting.

Following immune checkpoint inhibitor therapy.

Speaker 5: The incidence of this aggressive skin cancer in the US is estimated to be around 3000 patients in 2020 and is rising year on year.

The incidence of this aggressive skin cancer in the U S is.

Is estimated to be around 3000 patients in 2020 and is rising year on year.

Speaker 5: Between the years 2020 13, we note there was a 95% increase in reported cases.

Between the years 202013.

There was a 95% increase in reported cases.

Speaker 5: And this compares to 57% growth rates from melanoma and 15% for all solid tumour.

And this compares to 57% growth rate for melanoma and 15% for all solid tumors.

Due to the aging baby Boomer generation.

Speaker 5: Due to the aging baby boomer generation, the US incident that Merkel's self-cultonoma is expected to climb to 3,300 cases by 2025.

The U S incident that Merkel cell carcinoma is expected to climb to 3300 cases by 2025.

Speaker 5: Current standard of care in the US for patients with advanced or a current medical cell customer is with Pembra Lutumab or a value map. But there is no standard therapy for patients who progress on or a refractory to treatment with these immune checkpoint inhibitors.

Current standard of care in the U S. The patients with advanced or recurrent merkel cell carcinoma.

Is this temporary GMAT or value map, but there is no standard therapy for patients who progressed on or are refractory to treatment with these immune checkpoint inhibitors.

Speaker 5: or indeed for those patients who are ineligible to receive treatment with immunotherapy.

Or indeed for those patients who are ineligible to receive treatment with immunotherapy.

Speaker 5: Response rates and duration of response to chemotherapy in this setting are very low. And no survival benefit has been published from treatments in this setting.

Response rates and duration of response to chemotherapy in this setting a very light and no survival benefits has been published from treatments in this setting.

Speaker 5: We expect to commence our phase two study, the mantra three trial in mid 2022.

We expect to commence a phase III study the mantra three trial in mid 2022.

So to conclude some mantra, we have partnered with a key life is tacoma sites around the U S. Europe and elsewhere internationally, all with a strong track record of enrollment into life has to come at trials.

Speaker 5: that have concluded for Mantra, we have partnered with the key LiPUS ECOMA sites around the US, Europe , and elsewhere internationally, all with a strong track record of enrollment into LiPUS ECOMA trial.

Speaker 5: in the Manchutu Basket study, a selection of major academic sites with ready access to genomic testing and MDM2 copy number reporting, coupled with a large, potentially eligible patient population, should ensure rapid enrollment once the trial sites are all open.

And the amount of two basket study.

Selection of major academic site with ready access to genomic testing and MTN to copy number reporting.

Coupled with a large potentially eligible patient population should ensure rapid enrollment once the trial sites are all open.

Speaker 5: to mantra three, we have attracted the major national and international medical select experts to help develop our mantra three protocol and development strategy in this indication.

The mantra three we have attracted the major national and international medical experts to help develop our mantra three protocol in development strategy in this indication and.

Speaker 5: And we recently concluded an advisory board of renowned board leaders tweeting Merkel's subclass NEME, where they reiterated their excitement for milledemotron investigation in this setting.

And we recently concluded an advisory board a pronounced volt, either treating merkel cell carcinoma, where they reiterated their excitement familiar dermatitis investigation in this setting.

Speaker 5: Our dedicated team within RAIN continues to build personal relationships with all of our investigational sites around the world. And our selection of experienced oncology CROs equally committed to success will ensure we do all we can to develop a military-demotone as quickly as possible to patients.

Our dedicated team within rain continues to build personal relationships with all of our investigational sites around the world and our selection of experienced oncology Cri.

Equally committed to success will ensure we do all we can to develop <unk> as quickly as possible to patients.

Speaker 5: Let me now turn it over to our chief scientific officer, Dr Bob Doble. Bob.

Let me now turn it over to our Chief Scientific Officer, Dr. Bob Devil.

Bob.

Speaker 6: Thanks Richard, and good afternoon everyone. Since acquiring Milladamitana approximately one year ago, Rain's team has been working diligently to identify and validate the most relevant cancer populations for this MD-2 inhibitor.

Thanks, Richard and good afternoon, everyone since acquiring millet Allentown, approximately one year ago, bringing this team has been working diligently to identify and validate the most relevant cancer populations for the MDM two inhibitor.

Speaker 6: Our work has recently culminated in the presentation of multiple abstracts at recent conferences, including the AACR-NCI, ELRTC, virtual international conference on molecular targets and cancer therapeutics, or the triple conference. Highlighted in important pre-clinical collaborations with researchers around the world.

Our work has recently culminated in the presentation of multiple abstracts at recent conferences, including the ACR NCI E. R. T C virtual International conference on molecular targets and cancer therapeutics or the Triple conference highlighted an important preclinical collaborations with researchers around the world.

Speaker 6: We also hosted our first rain research and development day yesterday. This event featured both clinical and research experts who highlighted multiple opportunities for these in Miladana town in different tumor settings where MDM2 plays a critical role.

We also hosted our first rate in research and development day yesterday.

This event featured both clinical and research experts, who highlighted multiple opportunities for these had no downtime in different tumor settings, where <unk> plays a critical role.

Speaker 6: Let's turn to our conference presentations. First, Dr. Vijaya Tiranagaru, Senior Vice President and Head of Research at Raim, presented both pre-clinical and clinical data to support the use of milledamitants and patients with MDM2 amplification and wild-type P53.

Let's turn to our conference presentations first Dr. <unk> <unk> senior Vice President and head of research of rain presented both preclinical and clinical data to support the use of millet Amazon in patients with <unk> amplification and wild type <unk> 53.

Speaker 6: Pre-clinical models, including cancer cell lines, patient-derived organoids, and patient-derived zina graphs from numerous different solid-zumartites, demonstrated robust anti-tumor activity.

Preclinical models, including cancer cell lines and patient derived organoid in patient derived xenograft from numerous different solid tumor types demonstrated robust anti tumor activity.

Speaker 6: We also presented the rationale for our MDM2 amplification of at least 12 copies using a mutual exclusivity analysis in relation to P53 mutations from over 40,000 solid tumor patients derived from the AACR G&E database.

We also presented the rationale for our MGM two amplification of at least 12 copies using a mutual exclusivity analysis in relation to P 53 mutations.

From over 40000 in solid tumor patients derived from the ACR Genie database.

Speaker 6: Finally, clinical data from the phase one study in milidametin demonstrated three patients with breast cancer, synovial sarcoma, and small cell lung cancer with MDM2 amplification above the 12 copy number threshold all experiencing tumor regression and two of the three patients experiencing a partial response.

Finally clinical data from the phase one study of Mila downtown demonstrated three patients with breast cancer, synovial sarcoma, and small cell lung cancer with MDM two amplification above the 12 copy number of threshold all experiencing tumor regression and two of the three patients experiencing a partial response.

Speaker 6: These exciting data support the rationale for the Montreux 2 Basket Trips.

These exciting data support the rationale for the non trop two basket trial.

Also presented at the Triple Conference. So let's work from Dr. Caprio of lab at the Dana Farber Cancer Institute.

Speaker 6: Also presented at the Triple Conference was worked from Dr. DiCaprio's lab at the Dana-Farward Cancer Institute.

Speaker 6: the polyomavirus induces Merkel cell carcinoma in up to 80% of all Merkel cell cases and leads to overexpression of MDM2 and correlates with wild-type p53 steps.

The polymer virus induces merkel cell carcinoma, and up to 80% of all Merkel cell cases, and leads to overexpression of MDM too and correlates with wild type P 53 status.

Speaker 6: Dr. DiCaprio's presentation highlighted the potency of Noah Damatown and multiple in vitro and in vivo virus positive Mirkelfeld carcinoma model.

Dr. <unk> presentation highlighted the potency of no downtime in multiple in vitro and in vivo virus positive Merkel cell carcinoma models.

Speaker 6: This activity for Nolidamitant was P53 dependent as Nolidamitant induced gene expression of critical P53 targets, such as P21 and Puma.

This activity for North Amazon was P 53 dependent as Miliband, Montana induced gene expression of critical P 53 targets, such as <unk> 'twenty, one and Puma.

Speaker 6: The presentation also showed that knocking out P53 after a day that they affected Millet Amaz.

The presentation also showed that knocking out P 53, abrogated they affected melodramatize.

Speaker 6: It's exciting pre-connugal work formed part of the basis to prioritize a phase two trial for patients with Merkel-Felix-Carson-O-L.

This exciting preclinical work formed part of the basis to prioritize our phase II trial for patients with Merkel cell carcinoma.

Speaker 6: At our R&D day held yesterday, Dr. James DiCaprio also presented additional new patient-derived xenograft data from nilodamatin that exhibited compelling anti-tumor activity and tumor regression, which was not previously presented from his team's work at Dana-Farber.

At our R&D day held yesterday, Dr. James Dicaprio also presented additional new patient derived xenograft data from Alabama that exhibited compelling anti tumor activity in tumor regression, which was not previously presented from his teams work at Dana Farber.

Speaker 6: Further, Dr. Glenn Hanna gave an overview of the treatment landscape for Merkel cell carcinoma and highlighted the unmet need in the second line setting following the treatment with checkpoint inhibitors. The view offered in Merkel cell is that many patients don't respond in the front line setting with checkpoint inhibitors, and the second line setting offers very few options.

Further Dr. Glenn Hana gave an overview of the treatment landscape for Merkel cell carcinoma, and highlighted the unmet need in the second line setting following the treatment with checkpoint inhibitors.

Have you offered in Merkel cell is that many patients don't respond in the frontline setting where checkpoint inhibitors in the second line setting offers very few options.

Speaker 6: MDM2 inhibition is the only targeted strategy that is being evaluated in Merkle cell and it was great enthusiasm for its opportunity.

<unk> two inhibition is the only targeted strategy that is being evaluated in merkel cell and there was great enthusiasm for its opportunity.

Speaker 6: Brains are indeed a also feature several prominent clinical and research experts to highlight opportunities for North Amatane and several cancer

<unk> R&D. They also feature several prominent clinical and research experts to highlight opportunities for Miliband Matan and several cancer types, Dr. With FICO Gerry director of the Brown Cancer Center gave an overview of the MTM to P 53 axis highlighting the role for P 53, reactivation as an important anti cancer strategy. He stressed the non.

Speaker 6: Dr. Wafik Alderi, Director of the Brown Cancer Center, gave an overview of the MDM-2 P53 Act.

Speaker 6: highlighting the role for P53 activation as an important anti-cancer strategy. He stressed the non-overlapping strategies of restoring wild-type P53 activity, which is what we hope to do with Howard Amitant, via MDM2 inhibition, versus programs that target P53 meetings.

Overlapping strategies of restoring wild type P 53 activities, which is what we hope to do it with Amazon.

Amazon via MTM.

<unk> two inhibition versus programs that target P 53 minutes.

Speaker 6: He also noted the potential for combination of MDM2 inhibitors with immunotherapy strategies in cancer, given the association of MDM2 amplification with hyperpregression on checkpoint inhibitors.

He also noted the potential for combination of MD <unk> inhibitors with immunotherapy strategies in cancer, given the association of the MTM two amplification with hydro progression on checkpoint inhibitors.

Speaker 6: Additional speakers from MD Anderson, the Curious Institute, Italy's National Cancer Institute, and Memorial Fund Kettering all highlighted the rationale for the current plan strategies.

Additional speakers from MD Anderson, the Curie Institute, Italy's National Cancer Institute and Memorial Sloan Kettering, All highlighted the rationale for the current plan strategies for.

Speaker 6: for milidametan and several additional opportunities which are being considered by RAIN.

For mill of downtown and several additional opportunities, which are being considered Bahrain. These.

Speaker 6: These presentations provide support for RAIN's clinical strategy and prioritization of the differential light-blows Tacoma, an MDM-2 amplified agnostic tumor strategy, and Merkle cell carcinopathy. These presentations also help to provide the basis for exploration of clinical trials and other indications such as breast cancer and other large cancer populations.

These presentations provide support for <unk> clinical strategy and prioritization of Dedifferentiated, lipo sarcoma, and MDM to amplified agnostic tumor strategy and Merkel cell carcinoma. These presentations also helped to provide the basis for exploration of clinical trials and other indications such as breast cancer and other large cancer populations.

With that let me now turn it over to Nelson to review our financial results Nelson.

Speaker 6: With that, let me now turn it over to Nelson to review our financial results.

Speaker 5: Thank you Bob, and good afternoon everyone. I am pleased to provide an update for financial results for the third quarter of 2021. I would also like to invite you to review our Form 10Q file today for more details.

Thank you Bob and good afternoon, everyone I'm pleased to provide an update to our financial results for the third quarter of 2021.

Also like to invite you to review our Form 10-Q filed today for more details for the third quarter of 2021, we reported a net loss of $18 4 million compared to a net loss of $10 4 million in the third quarter of 2020.

Speaker 5: For the third quarter of 2021, we reported an net loss of $18.4 million compared to an net loss of $10.4 million in the third quarter of 2020. Research and development expenses were $15.3 million in the third quarter of 2021 as compared to $7.9 million in the third quarter of 2020.

Research and development expenses were $15 3 million in the third quarter of 2021 as compared to $7 9 million in the third quarter of 2020.

Speaker 5: The increase was firmly driven by the milestone fees to the Asia Sancho Company Limited of $5.5 million related to the initiation of a phase three clinical trial in DDLTS. RNG costs mainly for our lead candidate from the ongoing phase three pivotal mantra trial, as well as personal.

The increase was primarily driven by the milestone fees. The base you think you'll come in illuminate that a $5 5 million related to the initiation of our phase III clinical trial in Guinea Lts R&D cost mainly for our lead candidate from the ongoing phase III pivotal mantra trial I saw personal costs general.

Speaker 5: General and commercial expenses were 3.2 million for the third quarter of 2021, compared to 600,000 for the third quarter of 2020. The increase was primarily due to increases in various third-party GNA costs, including legal, outside consulting, accounting, and other fees, as well as personal costs.

And then most of these expenses were $3 2 million for the third quarter of 2021 compared to 600 person for the third quarter of 2020 <unk>.

The increase was primarily due to increases in various third party G&A costs, including legal and outside consulting accounting and audit fees as well as personnel costs.

Speaker 5: After September 30, 2021, Reign had 150.1 million in cash, cash equivalents and shorter investments, which provides funding to advance our research and development type.

As of September 32021 reign had the $150 1 million in cash cash equivalents and short term investments, which provides funding to advance our research and development pipeline.

Speaker 5: Also, as of September 30, 2021, Reign had approximately 26.5 million shares of Commerce Packout standing.

Also as of September 32021 reign had approximately $26 5 million shares of common stock outstanding.

Speaker 5: We continue to expect our full year 2021 operating spend to be approximately 50 million to 60 million and projected year end balance of approximately 137 million to 147 million in cash, cash equivalent and short term investments. With that, I'll now turn the poll over.

We continue to expect our full year 2021 operating spend to be approximately 50 million to $60 million and projected year end balance of approximately 137 million to one 7 million in cash cash equivalents and short term investments with that I'll now turn the call over bad niche.

Thanks, Nelson, let me now turn it back to the operator for a Q&A session.

Speaker 4: Thanks, Nelson. Let me now turn it back to the operator for a Q&A session.

Speaker 1: Thank you. Again, ladies and gentlemen, if you like that, if you have any questions, please press star or then one on your touchstone telepath. One moment, please.

Thank you again, ladies and gentlemen, if you'd like to ask a question. Please press Star then one when you touch tone telephone.

On the planet.

Speaker 1: Our first question comes from you, Gail, the top of it. A city group, you're lying.

Our first question comes when you get out of town.

Right.

Citigroup Your line is open.

Oh great.

Speaker 4: Great. Hi, I'm Anishin Seam. Thanks for taking the questions. I had a Q.

Team Thanks for taking the questions I had two.

Speaker 4: The first one is, could you be a bit more specific about what you found still compelling and recent non-synchal data from the data farmer who caused you to just place the triggers being asked trial and intmal sarcoma for the phase two in Markle's Del.

First one is could you be a bit more specific about what you found so compelling recent non clinical data from the Dana Farber caused you to displace the previously announced trial until sarcoma phase two in Merkel cell and.

Speaker 4: And the second question is sort of a strange question, but I was wondering, regarding the basket trial, what happens if you have multiple biopsies and you get heterogeneity and MDN2 copy number with some biopsies below and others above with the copy number of 12 threshold?

Question sort of a strange question, but I was wondering regarding the basket trial, what happens if he had multiple biopsies and you get heterogeneity in <unk>, Indiana to copy number with some biopsy below at other others.

Copy number of 12 threshold.

Yes.

Thanks, Joe I appreciate the question let.

Speaker 4: Thanks, you all. Appreciate the question. Let me turn the first question over to Bob, and ask which are the time I'm the second question.

Let me turn the first question over to Bob and ask Richard to chime in on the second question.

Speaker 6: Hi, you all. Thanks for the question. So in terms of the compelling data, you know, I think the biology of merclothol has been well understood for quite some time now in terms of the virus positive patients.

Hi, Yigal thanks for the question.

In terms of the compelling data you know I think the biology of Merkel cell has been well understood for quite some time now in terms of the virus positive patients.

Speaker 6: showing dependency on MDM 2 to red cancer cells of P53.

Showing dependency on MDM to read cancer cells or a P. 53, I think what we found compelling as for the first time, we were able to demonstrate in multiple preclinical models activity of melodrama town that was potent both cell line in patient derived xenograft models, including data that showed a significant.

Speaker 6: I think what we found compelling is for the first time we were able to demonstrate in multiple pre-clinical models activity of noidamitam that was potent in both cell line and patient-derived vision-graph models, including data that showed significant tumor regression.

Tumor regression.

Speaker 6: and patient drives the underground world. And so I think the rationale there is to move forward based on the biology and the unmet need in those multiple fellow patients.

Patient derived xenograft models.

And so I think the rationale there is to is to move forward based on the biology, and the unmet need in those market with all patients.

Speaker 5: And the second question related to potential externality.

And the second question related to potential heterogeneity.

Speaker 5: from sampling in terms of MDM-2 copy number.

I'm thinking in terms of MDM to copy number.

Speaker 5: in the basket study. So we have a, we will accept local testing as a criteria for entry. And so any sample that meets the criteria, any obviously sample that meets criteria MDM to copy number 12 or greater will be accepted. We do have retrospective testing at a central lab, which we've discussed before. And so all patients entering will have their tumors centrally tested and that will provide the homogeneity, if you like, across the site.

And in the basket study so we have a we will accept local testing.

The criteria for entry and so.

Hum.

Meets the criteria.

Something that meets the criteria MDM to copy number top of greater that will be accepted we do have retrospective testing at a central lab.

Which we've discussed before and so old patients entering we'll have that human is substantially tested and that will provide the.

How much of that if you like across the sites.

Speaker 5: And to some extent, we'll address potentially the heterogeneity that may be seen within sites. I don't know, Bob, but with your spin to run up to this, will you have anything to add to comments on that?

And to some extent will address potentially the heterogeneity that may be seeing with insights I don't know Bob with your expense in the run up to this but do you have anything to comment on that.

Speaker 6: Just that, you know, our belief is that like a lot of oncogenic drivers, this is likely an early event and the same way that P53 mutations are a very early event in cancer, those tend to be truncal and thus not display as much heterogeneity as non-relevant mutations in cancer.

Our belief is that like a lot of oncogenic drivers. This is likely in early about them. The same way. The P 53 mutations or very early about the cancer those tend to be Trump goal and does not have quite as much heterogeneity is non relevant mutations in cancer.

Alright, thank you.

Speaker 1: Next question comes from Michael Smith, the Chair Mr. Salana Co.

Thank you.

Our next question comes from Michael Schmidt.

Your line is open.

Speaker 7: Hi, good afternoon. This is EGAY on for Michael. Thanks for taking out a question.

Hi, Good afternoon. This is <unk> on for Michael Thanks for taking all the questions. We had a question on demand for two basket study. So based on the observed Asian M. D. M. Two amplification across different tumor types, how should we think of the mix.

Speaker 7: We had a question on the Mantra 2 basket study. So based on the observation of the MDM2 amplification across different tumor types, how should we think of the mix of the tumor types in this study? And perhaps related to this, what would be your registration strategy? Would you, for example, pick certain tumor types or are you going to consider a registration with a basket? Thank you.

The tumor types in the study and perhaps related to this what would be your registration strategy.

Would you for example peak certain tumor types or are you going to consider a registration with a basket.

Thanks, you gave for the question, let me turn it over to Richard.

Speaker 5: So yeah, thank you again for the question. The study is open to all human types. So at the present time, it's not restricted to any particular pathology. We know that some human types are likely to be more prevalent. That's very clear from the analysis of the various genomic databases that are out there. But there is no general cap on the methamphetamine. The expectation is that probably the top five humans will yield the most from the genomic databases. At present, the strategy is tumor agnostic. In other words, we expect to see a response that's across all tumors, regardless of the disease site. And biologically, that's rational. That's the oncogenic tumor driver and these...

Yes. Thank you again that so the question the.

The study is open to all tumor types at the present time, it's not restricted to any particular pathology.

We know that some too.

Tumor types that are likely to be more prevalent that's very clear.

In the analysis of the various databases that are out there.

But there is no general cat on limit demand and the expectation is that probably the top 500 humans, who will give them. The most from from the edge to edge basis.

At present.

<unk> is tumor agnostic in other words, we expect to see a response, that's across solid tumors and regardless of the disease site.

Biologically that's kind of rational that's the oncogenic catch human driver needs them.

Speaker 5: in these diseases.

In these diseases.

Speaker 5: As with everything, this is a signal seeking study. This is a basket study. We have the opportunity to look on an ongoing basis at the responses in the various tumultides and take action accordingly. But at the present time, we're sitting out with a pure tumultur agnostic approach. And we'll see where it goes.

As with everything. This is this is a signal seeking study. This is a basket study we have the opportunity to look at on an ongoing basis that at the responses in the various tumor types and take action accordingly, but at the present time, we're sitting out with a tumor agnostic approach and we'll see where it goes.

Speaker 4: And just add a little color there. So in terms of the top few tumor types, it would be long bladder, breast, and melanoma, which would be expected to yield the greatest number of patients with that copy number of 12 or greater. Just one. That's super out of it.

And just to add color their EBIT. So in terms of the top few tumor types would be lung bladder breast and melanoma, which would be would.

It would be expected to yield the greatest number of patients with that copy number 12 or greater.

Just wanted to Brad.

Yes.

Speaker 6: And just one final. I know there was a anecdotal data from the phase one trial in militant with high level endant amplification showing tumor regression in three different and very unique tumor types, the small cell lung cancer, breast cancer, and the sonovial sarcoma. So I'm evident already. How they.

Okay and just one final one sorry go ahead, there was different anecdotal data from the from the phase one trial in melanoma town with a high level and then two amplification showing tumor regressions.

In three different and very unique tumor types of small cell lung cancer breast cancer and a sanofi all sarcoma.

Some evidence already.

Got it that's super helpful. Thank you guys.

Thank you.

Speaker 1: Question comes and says can you start off by for family align so

Our next question comes from the South.

Kansas All of Piper Sandler Your line is open.

Speaker 8: Hey guys, thanks for taking my question. Maybe just one quick one for me that maybe sounds a little naive, but I know MDM2 amplification is considered universal in well-dipped D-diff LPS, but do you have a sense of the average copy number amplification that you see there and whether it frequently meets that threshold of being mutually exclusive with P53? And is there any plans as part of the mantra study to sort of retrospectively look at that? Thanks. Thanks, Joe. I enjoyed it.

Hey, guys. Thanks for taking my question, maybe just one quick one for me.

Maybe maybe sounds a little naive, but I know MDM to ample vacation is considered universal well 50, diff Lps, but do you have a sense of the average copy number amplification that you see there and whether it frequently meet that threshold.

Usually exclusive with P 53, and is there any planned as part of the mantra study to sort of retrospectively look at that.

Thanks, Joe I'll hand, it over to Bob.

Yes, thanks for the question Joe.

Speaker 6: So yes, we do know the average copy numbers for well-differentiated differentiated liposarcoma, for well-differentiated approximately 10 copies for de-differentiated liposarcoma, closer to 17 copies per cell, so pretty high level amplification in both populations. And as far as the mutual exclusivity, yes, this is a pattern that we see across many tumor types that we think have MDM2 dependency, and all of liposarcoma, sorry, all of well-differentiated differentiated liposarcoma, has a P53 mutation rate as low as 2%, so very, very rare P53 mutations compared to all cancers, which run around 50% of P53 mutated. So that relationship seems to hold up in multiple populations.

So yes, we do.

No the average copy numbers for a while different do you differentiate our lipo sarcoma for well difference approximately 10 copies for Dedifferentiated lipo, so come up closer to 17 copies per cell, so a pretty high level amplification both population.

And as far as the mutual exclusivity in the US. This is a pattern that we see across many tumor types that we think have MTM to dependency and in all of our lifeboat Sarcomas are all well definitely dedifferentiated lipo sarcoma has a <unk> three mutation rate as low as 2%. So very very rare P 53 mutations compared to.

All cancers, which run around 50%.

P 53, mutated so that that relationship seems to hold up in multiple populations.

Oh I'm sorry, the second part of the question was in terms of retrospective look yes, we are going to collect archival tumor samples and look at our MTM to copy number P 53 status and other biomarkers as well.

Speaker 6: Oh, and sorry, the second part of the question was in terms of retrospective look, yes, we are going to collect archival tumor samples and look at MDM2 copy number, P53 status, and other biomarkers as well in the mantra LPS study.

A L. P S study.

Speaker 8: Okay, got it. And if I could just maybe have a real quick follow up appreciating that you already have a pretty broad clinical development strategy, but what needs to happen to commit to exploring that you know, a GATA mutant ER positive signal that you've seen preclinically and...

Okay got it and if I could just maybe ask a real quick follow up the appreciating that you already have a pretty broad clinical development strategy, but what needs to happen to commit to exploring that get them in ER positive signal that you've seen.

Pre clinically and take that into the clinic.

Speaker 4: So, great question, Joel, I'll take that one. So, we are considering the data three continuously and we will articulate when we make a decision as to whether a company sponsored study or whether another manner of evaluation is going to be most appropriate for rain. But we're certainly taking into consideration the totality of our financial resources and the cash runway that we have to bear and we want to direct those resources towards the highest probability tumor type.

So great question, Joe I'll take that one so we are considering.

We gathered three continuously.

We will articulate when we make a decision as to whether a company sponsored study or whether in another manner of evaluation is going to be most appropriate for rain, but were certainly taking into consideration the totality of our financial resources and the cash runway that we have to bear and we want a direct those resources towards the highest probability tumor types.

Speaker 4: And those tumor types where we think that there's going to be a much clearer read on a registration path. So we're continuing to do work there, continuing to do a lot more work on mechanism as to what's going on with the GAT3 frameshift mutations and the sensitivity to MDM2 inhibition. And as we make that progress, we'll keep the street updated. Okay, got it. Yes, go ahead,

And those tumor types, where we think that theres going be much clear read on a registration path. So we're continuing to do work there continuing to do a lot more work on mechanism as to what's going on with the CAD III frameshift mutations and the sensitivity to <unk> inhibition.

And as we make that progress we'll keep keep.

Keep the street updated.

Okay got it that's clear thanks for taking my question.

Speaker 1: Thank you. Thank you. And I get a question from Karen Dinkert, the Goldman Sachs, a lot of both of them.

Thank you. Thank you.

Our next question comes from Corinne Jenkins Goldman Sachs. Your line is open.

Speaker 9: I get after a minute. So clearly you prioritize this mantra three study partly because it's a market opportunity, but can you just help us very not a little more specifically how you think about the size of that opportunity?

Speaker 4: I'll take that one. So, again, from the population statistics, around 3,000 patients, those are 2020 statistics. Richard did mention that this is a population that's growing far more quickly than the overall solid tumor population, given the primary demographic. Eighty percent of those patients are going to be MDM2 dependent based upon that viral positivity.

Speaker 4: And about a third of those patients are gonna be amenable to systemic therapy on an annual basis. We also know that from prior years of diagnosis, many of those patients with local disease are gonna become metastatic. So we ultimately derive a patient population of the amenable to systemic therapies per year of between 1,500 patients.

So we ultimately derive a patient population that the minimal systemic therapies per year of between 1500 patients.

Okay. That's really helpful and then I know it's.

Speaker 9: That's really helpful. And then I know it's still, you know, we just started this study, but in terms of the clinical bar for Mantra 2, how would you think about framing out the, kind of the clinical bar given it'll be a mix of tumor types and lines of study in that basket trial?

So.

Just started the study but in terms of the clinical bar for Mantech here, how would you think about framing out the.

The clinical bar, given it'll be a mix of tumor types and lines of studying that and not a basket trial.

Speaker 6: Sure, let me turn that over to Bob. Yeah, thanks for the question, Corinne. So the Chronicle Bar is quite low. You know, in discussing this indication with KOLs from across the country, there is really no second line standards following first line Pemberluzumab or a Velumab. So both checkpoint and hibiter therapies. You know, the second line prefers therapy.

Sure, Let me turn it over to Bob Thanks for the question Karen So the.

Gold bar is quite low.

In discussing this indication with kols from across the country. There is really no second line standard following first line <unk>.

<unk> or <unk>, so both checkpoint inhibitor therapies.

Second one.

Preferreds.

<unk>.

He is a clinical trial.

Speaker 6: And after that, a distance option is chemotherapy, which although it has decent response rates has incredibly short durability.

After that.

Distant option is chemotherapy, which although it has decent response rates has incredibly short durability, perhaps as low as in the range of three months.

Speaker 6: perhaps as low as in the range of three months. So the feedback from the Merkel cell KLO community is that response rate in the range of 15 to 20% and durability as low as four months may be meaningful in this patient population with limited options. Apologies, Queen. Was your question with regards to March 3 or March 2? Not your KLO.

So the feedback from the Mercury cell KOL community is that a response rate in the range of 15% to 20% and durability as low as four months.

Maybe a meaningful in this patient population with limited options.

Was your question with regards to the mantra three or mantra too.

Not your accounts.

Oh, sorry about that Karen.

All right.

Speaker 6: for mantra two, I think we don't fully know what the FDA would consider approval for an agnostic indication. There's only been three to date, Intractive Nebler, Trick Neb, and Pembrolysmab and MSI high patients. I think the feeling is that for patients who've exhausted most other cancer therapies that will respond straight in the range of 40% with durability.

For our mantra too I think we don't fully know what the FDA would consider approvable for an agnostic indication. There's only been three to date are <unk> and <unk> and MSI high patients.

I think the feeling is that for patients who have exhausted most of their cancer therapies that response rate in the range of 40% with durability.

Speaker 6: in the range of five to six months would probably be meaningful for patients who've exhausted standard of therapies, which is the criteria for our patients. But there aren't a lot of examples to be honest in terms of precedent.

And the range of five to six months would probably be meaningful for patients who are exhausted standard of care therapies, which is the criteria for our patients.

But there aren't a lot of examples to be honest in terms of a precedent.

Speaker 9: I just wanted to follow up, given the interim read, I'll be told about 12 months from now, do we expect the most likely response rates or will you be in position at that point given kind of case enrollment have at least early indicators of what durability of responses?

Yes.

One quick follow up given that.

Turn right out about 12 months from now do we expect them I think the response rates are well.

And at that point, given kind of states enrollment has.

Early indicators and what durability of responses.

Speaker 5: Yes, Richard, to take that one. Sure. So what we plan to do actually is have a meaningful follow-up. So we can quote not just the response rate but duration of response. And the likelihood is that we'll wait until we have about four months worth of follow-up data so that at least we know those responses are meaningful in terms of clinical durability.

Yes, Richard to take that one sure.

So what we plan to do actually have a meaningful last follow up.

So we can quote in not just the response rate the duration of response.

The the likelihood is that we'll wait till we have about four months with a follow up data so that at least we know those responses there.

Meaningful.

In terms of clinical labs durability.

That's helpful. Thank you.

I'm sorry.

Speaker 1: I'm showing no questions at this time. I'd like to turn the call back over to Evan Nees for launching for any closing remarks.

No questions at this time I'd like to turn the call back over to avenues for Lucky for any closing remarks.

Thank you and thanks to everyone for dialing in today, we look forward to giving you an update on our on our next quarterly results.

Speaker 4: Thank you and thanks to our one for for dialing you today. We look forward to giving you an update on our next quarterly results.

Thank you ladies and gentlemen, this does conclude today's conference. Thank you all for participating you may now disconnect have a great day.

Speaker 1: Ladies and gentlemen, this does include today's conference. Thank you all for participating. You may now just be next. Have a great day. Thank you all.

[music].

Speaker 1: Thank you for standing by and welcome to the RAIN Therapeutics third quarter 2021 Financial Results Conference call. At this time all participants are listening.

Thank you for standing by and welcome to the rain Therapeutics third quarter 2021 financial results Conference call. At this time, all participants on a listen only mode.

Speaker 1: After the speech is permutated, there will be a question and an answer session. To ask a question of that time, please press star then one when you catch shown telephs.

After the Speakers' presentation there'll be a question and answer session to ask a question at that time. Please press Star then one when your Touchstone telephone.

Speaker 1: As reminded today's conference hall is in recorded. I will now enter the conference hall. You host Mr. Bob Yettich, first, you may begin. Thank you operator. Good afternoon, everyone. With me today on the phone, I'll be in the next one. She's executive officer, Robert Dullbl, Chief Scientific Officer, Richard Bryce, Chief Medical Officer.

As a reminder, today's conference call is being recorded.

I would now like turn the conference host Mr. Bob yet for Covid again, Thank you operator and good afternoon.

Everyone with me today on the phone are of a nature Lunky Chief Executive Officer, Robert <unk>, Chief Scientific Officer, Richard Bryce Chief Medical Officer.

Speaker 3: Nelson Cabo-Tuan, team brace president of finance.

And Nelson covered Chuan senior Vice President of Finance.

Speaker 3: During today's call, Avonage will provide an overall business update. Which hurt will provide an update on rent.

During today's call <unk> will provide an overall.

Business update.

Richard will provide an update on <unk> clinical program.

Speaker 3: Bob will provide an update on research efforts, and Nelson will review the finance.

Bob will provide an update on research efforts and Nelson will review the financials.

Speaker 3: Before begin, I'd like to remind you that statements during this conference call that are not historical facts are for the statements within the meaning of the private Curious litigation reform act of 1995.

Speaker 3: These four of the statements are based on RAIN's current expectations and involve assumptions that we never materialize or prove to be correct.

These forward looking statements are based on <unk> current expectations and involve assumptions that may never materialize or prove to be correct.

Speaker 3: actual results could differ materially from those anticipated as such for the statements. As a result of various risks and uncertainties, as described in Reigns quarterly report, on form 10Q for the quarter ended March 31, 2021, and subsequent filings with Stearies and Exchange Commission.

And subsequent filings with Securities and Exchange Commission.

Speaker 3: All four of the key statements made during this conference call based on management's assumptions and estimates as of today. Do remember 10.

All forward looking statements made during this conference call based on management's assumptions and estimates as of today November 10th.

<unk> 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 it's my pleasure to turn the call over to nomination belonging CEO of reign of a niche.

Speaker 4: Thank you, Bob, and thanks to everyone for joining us for a third quarter earnings call. As a matter of principle for these earnings calls.

Speaker 4: We're going to make it standard practice to be very brief. We'll leave it to the Q&A to address the details that are the most interest in this most recent quarter and since the end of the third

Speaker 4: Wayne continues to advance the milademitin and RAD 52 programs forward. As a reminder, we'll continue to refer to milademitin as mila wherever appropriate.

<unk> forward as a reminder, we will continue to refer to <unk> as Miller wherever appropriate first and foremost are phase III trial. The mantra study for <unk> in patients with LIFO sarcoma is proceeding according to plan with sites being activated on a regular basis around the world as a potential registration enabling study.

Speaker 4: First and foremost, our phase three trial, the mantra study for Mila in patients with liposarcoma, is proceeding according to plan with sites being activated on a regular basis around the world. As a potential registration enabling study, there is no interim read with final data anticipated in 2023. Richard will provide some more color here.

There is no interim read with final data anticipated in 2023, Richard who will provide some more color here.

Speaker 4: Second, we also expect to dose our first patient in the phase two tumor agnostic mantra two study shortly, and we'll announce that when it happens. This trial will evaluate Miele in a tumor agnostic signal finding basket study across 65 patients in the US with solid tumors that exhibit a certain threshold of MDM2 gene amplification. We expect to provide an interim update for mantra two in the second half of next year.

We also expect to dose our first patient in the phase two tumor agnostic mantra to study shortly and we will announce that when it happens. This trial will evaluate <unk> in a tumor agnostic signal finding basket study across 65 patients in the U S with solid tumors that exhibit a certain threshold of MDM to gene amplification.

We expect to provide an interim update from mantra to in the second half of next year.

Third we announced that we will re prioritize our clinical strategy for third planned study towards Merkel cell carcinoma, replacing our prior planned studies intimal sarcoma. This new trial will be called mantra three <unk>.

Speaker 4: The decision to prioritize Merkel cell was made for three key reasons. One, new nonclinical data presented by the Dana Farber Cancer Institute demonstrating compelling efficacy for milledemotan, which already adds to the biologic rationale that many Merkel cell tumors are MDM3 dependent.

The decision to prioritize Merkel cell was made for three key reasons, one new non clinical data presented by the Dana Farber cancer Institute demonstrated compelling efficacy for <unk>, which already adds to the biologic rationale that many merkel cell tumors are MDM too dependent.

Speaker 4: We know there's already been presented signs of activity with MDM2 inhibition in Merkel cell from other MDM2 inhibitor programs.

Two we note theres already been presented signs of activity with <unk> inhibition in Merkel cell from other <unk> inhibitor programs.

Speaker 4: And three, the larger addressable market size of Mercosil as compared to Intimal Sarcoma, hence representing the most appropriate use of our financial resources.

And three the larger addressable market size of <unk> as compared to income will sarcoma, hence representing the most appropriate use of our financial resources based on the larger population of Merkel cell faster projected patient accrual rates and.

Speaker 4: Based on the larger population of Miracle Cell, faster projected patient accrual rates and an expected shorter crowd duration, the new plan Miracle Cell study has no significant impact on range cash runway.

And an expected shorter trial duration, the new planned Merkel cell study has no significant impact on <unk> cash runway.

Speaker 4: We expect mantra three to enroll 34 patients in the US in the second line or later settings amongst patients relapsed to checkpoint inhibitors, which is the standard of care in the frontline. And we expect to start the study in the middle of 2022.

Speaker 4: Finally, we held an R&D day yesterday where we hosted several prominent key opinion leaders across various treatment specialties where we think MDM2 inhibition could be applied.

Finally, we held an R&D day yesterday will be hosted several prominent key opinion leaders across various treatments specialties, where we think <unk> two inhibition could be applied speakers included Dr. Rafiq Geary from Brown University.

Speaker 4: Speakers included Dr. Wafik El-Diri from Brown University, who many of you may know for his discovery of P21.

Many of you may know for his discovery of $2 21, Dr <unk> and David Hong from Memorial Sloan Kettering, MD Anderson cancer centers, respectively, who will be participating in <unk> first two clinical studies for Miller and.

Speaker 4: Dr. Bernal Granger and David Haung from Memorial Sloan Kettering and MD Anderson Cancer Centers, respectively, who will be participating in range first two clinical studies for Mellup.

Speaker 4: and Dr. Glenn Hannah and James C. Taprio from Dana Farber for their expertise in Mirkelsselkars-Noma. We also included talks from Dr. Francois Clement-Bedard and Sylvia Stachiati who shed light on some additional clinical opportunities from the lab.

And Dr. Glenn Hana and James could caprio from Dana Farber for their expertise in Merkel cell carcinoma.

Also included talks from doctors Francois implement the guard and Sylvia stack, the Audi to shed light on some additional clinical opportunities for Miller.

Our strategy continues to be to focus our early effort on the most sensitive MDM too dependent tumor types first and will be followed by combination strategies to further enhance patient outcomes and other P. 53, wild type cancers, we're very excited about the potential for a range of opportunities for Miller has a meaningful impact.

Speaker 4: Our strategy continues to be to focus our early effort on the most sensitive MDM to depended tumor types first, and will be followed by combination strategies to further enhance patient outcomes and other P53 wild type cancer.

Speaker 4: We're very excited about the potential for a range of opportunities from Miller to have a meaningful impact on patient care.

On patient care.

Speaker 4: Last, the early preclinical work around programs targeting RAD52 continues to move forward, and we expect to provide updates at future scientific symposia as appropriate.

The early preclinical work around programs targeting <unk> continues to move forward and we expect to provide updates at future and future scientific symposia as appropriate.

Speaker 4: With that, I'd like to turn it over to our chief medical officer, Dr. Richard Brace.

With that I'd like to turn it over to our Chief Medical Officer, Dr. Richard Bryce.

Speaker 5: Thank you, Ebony, and good afternoon, everyone.

Kevin.

And good afternoon, everyone.

Speaker 5: Following on from our last earnings call at August , where we announced a start to our pivotal phase three mantra study, indeed, translated like the SACOMA, we are progressing the side activation throughout the US and Europe , anticipating approximately 30 sites to be opened by the end of the year with the remaining 45 sites in Europe , North America, and certain major Pacific countries coming on stream before the end of the first quarter 2022. Patients and Romans continue to...

Following on from our last earnings call. It August where we announced the stock to a pivotal phase III <unk> study indeed translated like the sarcoma, we are progressing with site activations throughout the U S and Europe anticipating approximately 30 sites to be opened by the end of the year with the remaining 45 site in Europe.

With America, and certain Asia Pacific countries coming on stream before the end of the first quarter 2022.

Patient enrollment continues as expected.

Speaker 5: I'm pleased to announce today that our second trial, the Mantra II basket study is now active and open to enrolment.

I am pleased to announce today that our second trial. The manager two basket study is now active and open to enrollment we will make a separate announcement when the first patient is dosed.

Speaker 5: we will make a separate announcement when the first patient is dose.

Speaker 5: We expected the Manchu-2 study will ultimately be opened in a total of approximately 10 sites throughout the United States, with additional just-in-time sites as necessary from the Tempest and Carousel referral.

Speaker 5: The study is open to patients that have p53 wild type and MDM2 amplified with a minimum gene copy number of 12 or six fold increase in copy number by local testing method.

The study is open to patients that are P 53, wild type and the MDM to amplified with a minimum gene copy number of 12 or six fold increase in copy number by local testing methods.

Speaker 5: As we previously discussed, this threshold is chosen because the hygiene amplification at these levels has been observed to exclude P53 mutations. They're by ensuring MDM2 as the oncogenic driver in these tumors.

As we previously discussed this threshold is chosen because the hygiene amplification that these levels has been observed to exclude P 53 mutations, thereby ensuring MDM too as the oncogenic driver in these tumors.

Speaker 5: As well as the in-house genomic screening at the selected US site, we have partnered with Tempest and Carous for a follow-up patient meeting these particular criteria.

As well as the in house genomics screening at the selected U S sites we.

We have partnered with 10% tariffs peripheral if patients meet the needs particular criteria.

Speaker 5: The study aims to enroll 65 patients across a range of solid tumors. And the treatment protocol is the same as in the Registrational Mantra study.

The study aims to enroll 65 patients across a range of solid tumors.

And the treatment protocol is the same as in the Registrational mattress study.

Speaker 5: That is 260 milligrams orally, once daily for three consecutive days out of 14.

That is 260 milligrams orally once daily for three consecutive days out of 2014.

Speaker 5: And as we previously advised, we anticipate an inter-analysis and data readout in the second half of next year.

And as we previously advised we anticipate an interim analysis and data readout in the second half of next year.

Speaker 5: As I've been each mentioned, we have deprioritized our Intimal SIR KOMA program to focus on the opportunity in Merkel-Selcast NOMA in the second line setting. Following MUNE checkpoints,

Does that have any just mentioned we have deep prioritize our internal sarcoma program to focus on the opportunity in Merkel cell carcinoma in the second line setting.

Blowing immune checkpoint inhibitor therapy.

Speaker 5: The incidence of this aggressive skin cancer in the US is estimated to be around 3000 patients in 2020 and is rising year on year.

The incidence of this aggressive skin cancer in the U S.

Is estimated to be around 3000 patients in 2020 and is rising year on year.

Speaker 5: Between the years 2020 13, we note there was a 95% increase in reported cases.

Between the years 2000, and 2013, we note there was a 95% increase in reported cases.

Speaker 5: And this compares to 57% growth rates from Elanoma and 15% for all solitum.

And this compares to 57% growth rate for melanoma and 15% for all solid tumors.

Due to the aging baby Boomer generation.

Speaker 5: Due to the aging baby boomer generation, the US incidence of Merkel-South Kassnomer is expected to climb to 3,300 cases by 2025.

The U S incidents that Merkel cell carcinoma is expected to climb to 3300 cases by 2025.

Speaker 5: Current standard of care in the US for patients with advanced or a current medical cell counselor is with Pembra Lutumab or a value map. But there is no standard therapy for patients who progress on or a refractory to treatment with these immune checkpoint inhibitors.

Current standard of care in the U S for patients with advanced or recurrent Merkel cell carcinoma.

As of September <unk>, our value map, but there is no standard therapy for patients who progress on or are refractory to treatment with these immune checkpoint inhibitors.

Speaker 5: or indeed for those patients who are ineligible to receive treatment with immunotherapy.

Or indeed for those patients who are ineligible to receive treatment with immunotherapy.

Speaker 5: Response rates and duration of response to chemotherapy in this setting are very low. And no survival benefits has been published from treatments in this setting.

Response rates and duration of response to chemotherapy in this setting are very low and no survival benefits has been published from treatments in this setting.

Speaker 5: We expect to commend the phase two study, the mantra three trial in mid 2022.

We expect to commence a phase III study the mantra three trial in mid 2022.

Speaker 5: that is conclude for Mantra. We have partnered with the key LiPUS ECOMA sites around the US, Europe , and elsewhere internationally, all with a strong track record of enrollment into LiPUS ECOMA trial.

So to conclude some mantra, we have partnered with the key licensed Tacoma sites around the U S. Europe and elsewhere internationally, all with a strong track record of enrollment into like us to come of trials.

And the managed two basket study.

Selection of major academic site with ready access to genomic testing and MDM to copy number reporting.

Coupled with a large potentially eligible patient population should ensure rapid enrollment once the trial sites are all open.

Speaker 5: the mantra three, we have attracted the major national and international medical selects births to help develop our mantra three protocol and development strategy in this indication.

The mantra three we have attracted the major national and international medical sell experts to help develop our mantra three protocol in development strategy in this indication and.

Speaker 5: And we recently concluded an advisory board of renowned thought leaders treating Merkel-Celkasten Emma, where they reiterated their excitement for Mila Demetine investigation in this setting.

And we recently concluded an advisory board a pronounced thought leaders treating merkel cell carcinoma, where they reiterated their excitements familiar demeton investigation in this setting.

Our dedicated team within rain continues to build personal relationships with all of our investigational sites around the world.

And our selection of experienced oncology cra's equally committed to success will ensure we do all we can to develop melodramatize as quickly as possible for patients.

Speaker 5: Let me now turn it over to our chief scientific officer, Dr Bob Doble. Bob.

Let me now turn it over to our Chief Scientific Officer, Dr. Bob <unk>.

Yes.

Thanks, Richard and good afternoon, everyone since acquiring millet Allentown, approximately one year ago <unk> team has been working diligently to identify and validate the most relevant cancer populations for the <unk> inhibitor.

Speaker 6: Our work has recently culminated in the presentation of multiple abstracts at recent conferences, including the AACR NCI EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics, or the TRBL Conference, highlighted important preclinical collaborations with researchers around the world.

Our work has recently culminated in the presentation of multiple abstracts at recent conferences, including the ACR NCI EUR Tc virtual International conference on molecular targets and cancer therapeutics or the Triple conference highlighted an important preclinical collaborations with researchers around the world.

Speaker 6: We also hosted our first rain research and development day yesterday. This event featured both clinical and research experts who highlighted multiple opportunities for these in the Audana town in different tumor settings where MDM2 plays a critical role.

We also hosted our first rating research and development day yesterday.

This event featured both clinical and research experts, who highlighted multiple opportunities for these had no downtime in different tumor settings, where <unk> plays a critical role.

Speaker 6: Let's turn to our conference presentations. First, Dr. Vijaya Tiranagaru, senior vice president and head of research at RAIN presented both preclinical and clinical data to support the use of millibamitants and patients with MDM2 amplification and wild-type P53.

Let's turn to our conference presentations first Dr. <unk> <unk> senior Vice President and head of research at Ram presented both preclinical and clinical data to support these in millet Amazon in patients with <unk> amplification and wild type <unk> 53.

Speaker 6: Pre-clinical models, including cancer cell lines, patient-derived organoids, and patient-derived zina graphs from numerous different solid-zumartites demonstrated robust anti-tumor activity.

Preclinical models, including cancer cell lines patient derived organoid and patient derived xenograft from numerous different solid tumor types demonstrated robust anti tumor activity.

Speaker 6: We also presented the rationale for our MDM2 amplification of at least 12 copies using a mutual exclusivity analysis in relation to P53 mutations. From over 40,000 cell and tumor patients derived from the AACR Genie database.

We also presented the rationale for our MDM two amplification of at least 12 copies using a mutual exclusivity analysis in relation to P. 53 mutations from over 40000 solid tumor patients derived from the ACR Genie database.

Speaker 6: Finally, clinical data from the Phase I study in Milladamitant demonstrated three patients with breast cancer, synovial sarcoma, and small cell lung cancer, with MDM2 amplification above the 12 copy number threshold, all experiencing tumor regression and two of the three patients experiencing a partial response. These exciting data support the rationale for the Mounder II basket trial.

These exciting data support the rationale for the mantra two basket trial.

Also presented at the Triple Conference. So let's work from Dr. Caprio of lab at the Dana Farber Cancer Institute.

Speaker 6: Also presented at the triple conference was work from Dr. DiCaprio's lab at the Dana-Farber Cancer Institute.

Speaker 6: polyomavirus induces mercol cell carcinoma and up to 80% of all mercol cell cases and leads to overexpression of MDN2 and correlates with wild type P53 stuff.

Polymer virus induces merkel cell carcinoma, and up to 80% of all Merkel cell cases, and leads to over expression of <unk> and correlates with wild type <unk> three status.

Speaker 6: Dr. DiCaprio's presentation highlighted the potency of Noah Damatown in multiple in vitro and in vivo virus positive Miraclecell carcinoma model.

Dr. <unk> presentation highlighted the potency of north out of town in multiple in vitro and in vivo virus positive Merkel cell carcinoma models with.

Speaker 6: This activity for Nolidamitant was P53 dependent as Nolidamitant induced gene expression of critical P53 targets, such as P21 and Puma.

This activity for millet, Amazon was P 53 dependent as Noah that Montana induced gene expression of critical P 53 targets, such as <unk> 'twenty, one and Puma.

Speaker 6: The presentation also showed that knocking out P53 abrogated the effect of the

Presentation also showed that knocking out P 53, abrogated they affected mill with Amazon.

Speaker 6: This exciting pre-connugal work formed part of the basis to prioritize a phase 2 trial for patients with mercol-fell carcinolum.

This exciting preclinical work formed part of the basis to prioritize our phase II trial for patients with Merkel cell carcinoma.

Speaker 6: At our R&D day held yesterday, Dr. James DiCaprio also presented additional new patient-derived xenograft data from the Lidamitab that exhibited compelling anti-tumor activity and tumor regression, which was not previously presented from his team's work at Dana-Farber.

At our R&D day held yesterday, Dr. James to Capri, I'll also presented additional new patient derived xenograft data from Alabama town that exhibited compelling anti tumor activity in tumor regression, which was not previously presented from his teams work at Dana Farber.

Speaker 6: The view offered in Merkel's cell is that many patients don't respond in the front line that it would checkpoint inhibitors. And the second line that it offers very few options.

Have you offered in Merkel cell is that many patients don't respond in the frontline setting with checkpoint inhibitors in the second line setting offers very few options.

Speaker 6: MDM2 inhibition is the only targeted strategy that is being evaluated in Merkel's cell and there was great enthusiasm for its opportunity.

<unk> inhibition is the only targeted strategy that is being evaluated in merkel cell and there was great enthusiasm for its opportunity.

Speaker 6: Brains are indeed a, also features several prominent clinical and research experts to highlight opportunities for North Amatane and several cancer types.

Raines R&D. They also featured several prominent clinical and research experts to highlight opportunities for north Amazon and several cancer types. Dr. <unk> director of the Brown Cancer Center gave an overview of the MTM to P 53 axis highlighting the role for <unk> three reactivation as an important anti cancer strategy. He stressed the non.

Speaker 6: Dr. Wafik Alderi, Director of the Brown Cancer Center, gave an overview of the MDM-2 P53 Act.

Speaker 6: highlighting the role for P53 activation as an important anti-cancer strategy. He stressed the non-overlapping strategies of restoring wild-type P53 activity, which is what we hope to do with Howard Amitem, via MDM2 inhibition, versus programs that target P53 meetings.

Overlapping strategies of restoring wild type <unk> three activity, which is what we hope to do it with Amazon.

Amazon via MDM to inhibition versus programs that target P 53 minutes.

Also noted the potential for combination of <unk> inhibitors with immunotherapy strategies in cancer, given the association of MDM, two amplification with hydro progression on checkpoint inhibitors.

Speaker 6: Additional speakers from MD Anderson, the Curie Institute, Italy's National Cancer Institute, and Memorial Fund Kettering all highlighted the rationale for the current plan strategies.

Additional speakers from MD Anderson Curie Institute it always.

National Cancer Institute and Memorial Sloan Kettering, all highlighted the rationale for the current planned strategies.

Speaker 6: for Mill of Damatown and several additional opportunities which are being considered by rain.

Per mill of downtown and several additional opportunities, which are being considered by rain.

Speaker 6: These presentations provide support for RAIN's clinical strategy and prioritization of the differential light-blows Tacoma, an MDM-2 amplified agnostic tumor strategy, and Merkle cell carcinoma. These presentations also help to provide the basis for exploration of clinical trials in other indications such as breast cancer and other large cancer populations.

These presentations provide support for a range of clinical strategy and prioritization of Dedifferentiate, LIFO sarcoma, and MDM to amplified agnostic tumor strategy and Merkel cell carcinoma. These presentations also helped to provide the basis for exploration of clinical trials and other indications such as breast cancer and other large cancer populations.

Speaker 6: With that, let me now turn it over to Nelson to review our financial results.

With that let me now turn it over to Nelson to review our financial results Nelson.

Speaker 5: Thank you, Bob, and good afternoon, everyone. I am pleased to provide an update for financial results for the third quarter of 2021. I would also like to invite you through a viewer form 10Q file today for more details.

Thank you Bob and good afternoon, everyone.

I'm pleased to provide an update to our financial results for the third quarter of 2021 I would also like to invite you to review our Form 10-Q filed today for more details for the third quarter of 2021, we reported a net loss of $18 4 million compared to a net loss of $10 4 million in the third quarter of 2012.

Speaker 5: For the third quarter of 2021, we reported a net loss of $18.4 million compared to a net loss of $10.4 million in the third quarter of 2020. Research and development expenses were $15.3 million in the third quarter of 2021 as compared to $7.9 million in the third quarter of 2020.

<unk>.

Research and development expenses were $15 3 million in the third quarter of 2021 as compared to $7 9 million in the third quarter of 2020.

Speaker 5: The increase was firmly driven by the milestone fees to the Asia Sancho Company Limited of $5.5 million related to the initiation of a phase three clinical trial and DDLTS. RNG costs mainly for our lead candidate from the ongoing phase three pivotal mantra trial, as well as personal.

The increase was primarily driven by the milestone fees of Asia Company <unk> of $5 5 million related to Dennis station of our phase III clinical trial in Guinea Lts R&D cost mainly for our lead candidate from the ongoing phase III pivotal mantra trial <unk> personal costs.

General and administrative expenses were $3 2 million for the third quarter of 2021 compared to 600000 for the third quarter of 2020 they.

The increase was primarily achieved through increases in various third party G&A costs, including legal and outside consulting accounting and audit fees as well as personnel costs.

Speaker 5: After September 30, 2021, Reign had 150.1 million in cash, cash equivalents and short-term investments, which provides funding to advance our research and development type.

As of September 32021, <unk> had $150 1 million in cash cash equivalents and short term investments, which provides funding to advance our research and development pipeline.

Speaker 5: Also, as of September 30, 2021, RAINN had approximately 26.5 million shares of common stock outstanding.

Also as of September 32021, <unk> had approximately $26 5 million shares of common stock outstanding.

Speaker 5: We continue to expect our full year 2021 operating spend to be approximately 50 million to 60 million projected year and balance of approximately 137 million to 147 million in cash cash equivalence and short term investments. With that, I will now turn the call over.

We continue to expect our full year 2021 operating spend to be approximately 50 million to $60 million in projected year end balance of approximately $137 million to $1 7 million in cash cash equivalents and short term investments with that I'll now turn the call over back to <unk>.

Speaker 4: Thanks, Nelson. Let me now turn it back to the operator for a Q&A session.

Thanks, Nelson, let me now turn it back to the operator for our Q&A session.

Speaker 1: Take it. Again, ladies and gentlemen, if you like that, if you have any questions, please press star then one on your touchstone telepath. One moment, please.

Thank you again, ladies and gentlemen, if you'd like to ask a question. Please press Star then one when your Touchstone telephone one moment please.

Speaker 1: Our first question comes from you, Gail, the top of it. A city group, you're lying.

Our first question comes when you get out the top of it.

Citigroup Your line is open.

Speaker 8: Great. Hi, I'm Anishin Singh. Thanks for taking the questions. I had two.

Great.

<unk>, thanks for taking the questions I had two.

Speaker 8: The first one is, could you be a bit more specific about what you found so compelling and recent non-punicle data from the data fiber because you just placed the triggers being asked to trial on intmal sarcoma for the phase two and Markle's doubt?

First one is could you be a bit more specific about what you found so compelling recent non clinical data from the Dana Farber caused you to displace to previously announced trial and install sarcoma for the phase two in Merkel cell and the second question sort of a strange question, but I was wondering regarding the basket trial, what happens if you have multiple <unk>.

Speaker 8: And the second question, it's a bit of a strange question, but I was wondering, regarding the basket trial, what happens if you have multiple biopsies and you get heterogeneity in MD and MD and MD and 2 copy number with some biopsies below and others above the copy number of 12 thresholds?

And you get heterogeneity in Nvme nvme to copy number with some biopsies below at other others above the.

Copy number of 12 threshold.

Thanks.

Speaker 4: Thanks, you go. Appreciate the question. Let me turn the first question over to Bob and ask which are the time on the second question.

Thanks I appreciate the question let.

Let me turn the first question over to Bob and ask Richard to chime in on the second question.

Speaker 6: Hi, you all. Thanks for the question. So in terms of the compelling data, you know, I think the biology of merclothol has been well understood for quite some time now, in terms of the virus positive patients.

Hi, Yigal thanks for the question.

In terms of the compelling data you know I think the biology of Merkel cell has been well understood for quite some time now in terms of the virus positive patients.

Speaker 6: showing dependency on MDM-2 to red cancer cells of P53.

Showing dependency on MDM too to rid cancer cells. The P 53, I think what we found compelling as for the first time, we were able to demonstrate in multiple preclinical models activity of melodrama Tam that was potent in both cell lines and patient derived xenograft models, including data that showed a significant.

Speaker 6: I think what we found compelling is for the first time we were able to demonstrate in multiple pre-connacle models activity of noidamitam that was potent in both cell line and patient derived vision and graph models, including data that showed significant tumor regression.

Tumor regression.

Speaker 6: and patient drives the underground world. And so I think the rationale there is to move forward based on the biology and the unmet need in those multiple fellow patients.

Patient derived xenograft models.

And so I think the rationale there is to is to move forward based on the biology and the unmet need in those market will help patients.

Speaker 10: And the second question related to potential heterogeneity.

And the second question related to potential heterogeneity.

Speaker 10: from sampling in terms of MDM-2 copy number.

Im saying in terms of MDM to copy number.

Speaker 10: in the basket study. So we have a, we will accept local testing as a criteria for entry. And so any sample that meets the criteria, any capacity sample that meets criteria, MDM to a copy number 12 or greater, will be accepted. We do have retrospective testing at a central lab, which we've discussed before. And so all patients entering will have that tumor centrally tested and that will provide the homogeneity if you like across the site.

And in a basket study so we have that we will.

Except local testing.

The criteria for entry and so.

Some called it.

Meets the criteria.

We see something that meets the criteria MDM to copy number top of greater will be accepted we do have retrospective testing at a central lab.

Which we've discussed before and so old patients entering we'll have that tumors substantially tested and that will provide the.

<unk>, if you like across the sites.

Speaker 10: And to some extent we'll address potentially the heterogeneity that may be seen within sites. I don't know if Bob, but with your spin to run up to this, will you have anything further to comment on that?

And to some extent will address potentially the heterogeneity that may be seeing with insights I don't know Bob with just Vince in the run up to this whether you have anything to those comments on that.

Speaker 6: Just that, you know, our belief is that like a lot of oncogenic drivers, this is likely an early event. And the same way that P53 mutations are very early event in cancer, there's tend to be trunkal and thus not disquay as much heterogeneity as non-relevant mutations in cancer.

<unk>.

Our belief is that like a lot of oncogenic drivers.

Likely an early event in the same way that P. 53 mutations are very early about the cancer those tend to be <unk>.

Not quite as much heterogeneity is non relevant mutations in cancer.

Alright, thank you.

Thank you. Our next question comes from Michael Schmidt.

Speaker 1: education cooked

Your line is open.

Speaker 7: Hi, good afternoon. This is EGAY on for Michael. Thanks for taking out a question.

Hi, Good afternoon. This is <unk> on for Michael Thanks for taking all the questions. We had a question on the mantra two basket study. So based on the observed <unk> M. D M. Two amplification across different tumor types.

Speaker 7: We had a question on the Mantra II basket study. So based on the observation of the MDM II amplification across different tumor types, how should we think of the mix of the tumor types in this study? And perhaps related to this, what would be your registration strategy? Would you, for example, pick certain tumor types or even consider a registration with a basket? Thank you.

How should we think of the mix.

The tumor types in the study and.

Perhaps related to this what would be your registration strategy.

Would you for example peak certain tumor types or are you going to consider a registration.

Basket. Thank you.

Thanks, you gave for the question, let me turn it over to Richard.

Speaker 10: So, yeah, thank you again for the question. The study is open to all tumor types. So at the present time, it's not restricted to any particular pathology. We know that some tumor types are likely to be more prevalent. That's very clear from the analysis of the various genomic databases that are out there. But there is no general cap on them at the moment. The expectation is that probably the top five tumors will yield the most from the genomic databases. At present, the strategy is tumor agnostic. In other words, we expect to see a response that's across all tumors, regardless of the disease site. And, you know, biologically, that's kind of rational. That's the oncogenic tumor driver in these.

So yes. Thank you again for the question.

The study is open to all tumor types at the present time, it's not restricted to any particular pathology.

No that test.

Tumor types.

Likely to be more prevalent that's very clear.

From the analysis of the various databases that are out there and but there is no general cap on limit them and the expectation is that probably the top five two months, we'll give them the most from from the edge to edge spaces.

At present.

<unk> is tumor agnostic in other words, we expect to see a response a crossover tumors.

The <unk> site.

Biologically that's kind of rationale that's the oncogenic driver needs them.

Speaker 10: in these diseases.

In these diseases.

Speaker 10: As with everything, this is a signal seeking study. This is a basket study. We have the opportunity to look on an ongoing basis at the responses in the various tumultides and take action accordingly. But at the present time, we're sitting out with a pure tumultive agnostic approach and we'll see where it goes.

As with everything. This is this is a signal seeking study. This is a basket study we have the opportunity to look at.

On ongoing basis that at the responses in the various tumor types and take action accordingly, but at the present time was sitting out there.

Tumor agnostic approach.

And we'll see where it goes.

Speaker 4: And just to add a little color there, so in terms of the top few tumor types would be lung, bladder, breast and melanoma, which would be would be expected to yield the greatest number of patients with that copy number 12 or greater.

And just to add color their EBIT.

So in terms of the top few tumor types would be lung bladder breast and melanoma, we should be.

It would be expected to yield the greatest number of patients with that copy number 12 or greater.

And just wanted to.

Yeah.

Speaker 6: And just one final note. There was anecdotal data from the phase one trial of milidametan with high level and DMT amplification showing tumor regressions and three different and very unique tumor types of small cell lung cancer, breast cancer, and a synovial sarcoma. So some evidence already. Thank you.

Okay, and just one final one sorry go ahead.

Anecdotal data from the from the Phase one trial in melanoma town with a high level on them two amplification showing tumor regression.

In three different and very unique tumor types of small cell lung cancer breast cancer and the synovial sarcoma. So.

Some evidence already.

Got it that's super helpful. Thank you guys.

Thank you.

Speaker 1: Our next question comes from Joe Cantizaro of Piper Family, Alonzo.

Our next question comes from the South Kansas.

Piper Sandler your line is open.

Speaker 8: Hey, guys, thanks for taking my question. Maybe just one quick one for me that maybe sounds a little naive, but I know MDM2 amplification is considered universal in well-dipped D-diff LPS. But do you have a sense of the average copy number amplification that you see there and whether it frequently meets that threshold of being mutually exclusive with P53? And is there any plans as part of the mantra study to sort of retrospectively look at that? Thanks. Thanks, Joe. I'll hand it over to Bob.

Hey, guys. Thanks for taking my question, maybe just one quick one for me.

Maybe maybe sounds a little naive, but I know MDM two amplification is considered universal in wealth ft Lps, but do you have a sense of the average copy number amplification that you see there and whether it frequently meets that threshold of being usually exclusive with P. 53 and is there any planned as part of the mantra study.

Two sort of retrospectively look at that.

Thanks, Joe I'll hand, it over to Bob.

Yes, thanks for the question Joe.

Speaker 6: So yes, we do know the average copy numbers for well-differentiated liposarcoma. For well-differentiated, it's approximately 10 copies. For de-differentiated liposarcoma, it's closer to 17 copies per cell, so a pretty high level amplification in both populations. And as far as the mutual exclusivity, yes, this is a pattern that we see across many tumor types that we think have MDM2 dependency, and all of liposarcoma, sorry, all of well-differentiated liposarcoma has a p53 mutation rate as low as 2%. So very, very rare p53 mutations compared to all cancers which, you know, run around 50% p53 mutated. So that relationship seems to hold up in multiple populations.

So yes, we do.

No the average copy numbers for a while different do differentiate a LIFO sarcoma for well difference approximately 10 copies for Dedifferentiated lipo sarcoma up closer to 17 copies per cell, so a pretty high level amplification in both population.

And as far as the mutual exclusivity. The us. This is a pattern that we see across many tumor types that we think have MDM to dependency in all of our LIFO sarcoma, sorry, all of well differ Dedifferentiated Lipo sarcoma has a <unk> three mutation rate as low as 2%. So very very rare P 53 mutations compared to.

All cancers, which run around 50%.

P 53 mutated so.

That relationship seems to hold up in multiple populations.

Speaker 6: Oh, and that's the second part of the question was in terms of retrospective look, yes, we are gonna collect archival tumor samples and look at MDM2 copy number P53 status and other biomarkers as well in the mantra LPS study.

Oh I'm sorry, the second part of the question was in terms of retrospective look yes, we are going to collect archival tumor samples and look at our MDM to copy number P 53 status and other biomarkers as well.

L P off study.

Speaker 8: Okay, got it. In fact, I could just maybe have a real quick follow up appreciating that you already have a pretty broad clinical development strategy, but what needs to happen to commit to exploring the, you know, a GAT immune ER positive signal that you've seen preclinically and...

Pre clinically and take that into the clinic.

Speaker 4: So, great question, Joel, take that one. So, we are considering the data tree continuously. And we will articulate when we make a decision as to whether a company sponsored study or whether another manner of evaluation is going to be most appropriate for rain. But we're certainly taking into consideration the totality of our financial resources and the cash runway that we have to bear. And we want to direct those resources towards the highest probability tumor type.

So great question and I will take that one so we are considering.

<unk> three continuously.

We will articulate when we make a decision as to whether a company sponsored study or whether in another manner of evaluation is going to be most appropriate for rain, but we've certainly taken into consideration the totality of our financial resources and the cash runway that we have to bear and we want a direct those resources towards.

The highest probability tumor types.

Speaker 4: And those two times where we think that there's going to be much clearer read on a registration path. So we're continuing to do work there, continue to do a lot more work on mechanism as to what's going on with the Gatthree Frameship mutations and the sensitivity to MD into an ambition. As we make that progress, we'll keep the street updated.

And those tumor types, where we think that there's going to be much clear read on a registration path. So we're continuing to do work there continuing to do a lot more work on mechanism as to what's going on with the CAD III frameshift mutations in the sensitivity <unk> two inhibition.

And as we make that progress we'll keep.

Keep the street updated.

Okay got it that's clear thanks for taking my questions.

Thank you. Thank you.

Speaker 1: Thank you. Thank you. And next question comes from Karen Dinkert, the Goldman Sachs in Laudibovans.

Our next question comes from Luca <unk> Goldman Sachs. Your line is open.

Speaker 9: I get after a year and so clearly you prioritize this mantra three study partly because it's a market opportunity but can you just help us very much a little more specifically how you think about the size of that opportunity.

Hi, Good afternoon, clearly prioritizes manager three study, partly because of the market opportunity, but can you just help us frame out a little more specifically how do you think about the size of that opportunity.

Sure happy to I will take that one.

Speaker 4: We're happy to take that one. So again, from the population statistics around 3000 patients, those are 2020 statistics, Richard did mention that this is a population that's growing far more quickly than the overall solid tumor population given the primary demographic. 80% of those patients are gonna be MDM2 dependent based upon that viral positivity.

Again from the population statistics around 3000 patients. Those are 2020 statistics Richard did mention that this is a population that's growing far more quickly than the overall solid tumor population given the the primary demographic 80% of those patients are going to be MDM too dependent based upon that viral positivity.

And about a third of those patients are going to be.

Amenable to systemic therapy on an annual basis, we also know that from prior year.

Years of diagnosis many of those patients with local disease are going to become metastatic. So we ultimately derive a patient population that's a minimal systemic therapies per year of between 1500 patients.

Speaker 9: and then I know it's still, you know, we just started this study, but in terms of the clinical bar for Manchur2, how would you think about framing out the clinical bar given it'll be a mix of tuberculosis in line with study and that in that basket try?

Okay. That's really helpful. And then I know, it's so you know we just started the study but in terms of the clinical bar for me in check here, how long do you think about framing out the.

Given that it will be a mix of tumor types and lines of studying that and that that will get you.

Kyle.

Speaker 4: Sure, let me turn that over to Bob. Yeah, thanks for the question, Corinne. So the clinical bar is quite low. You know, and discussing this indication with KOLs from across the country, there is really no second line standard following first line Pemberluzumab or a value map. So both checkpoint and hibiter therapies. You know, the second line prefers therapy for therapy. ??? tools hope for cases taken.

Sure, Let me turn it over to Bob Thanks for the question Karen So the.

The clinical bar is quite low.

And discussed in this indication with Kols from across the country. There is really no second line standard following first line <unk>.

<unk> or <unk>, so both checkpoint inhibitor therapies.

The second one.

Preferreds.

He is the clinical trial.

Speaker 6: And after that, a distance option is chemotherapy, which although it has decent response rates has incredibly short durability.

And after that.

A distant <unk>.

Option is chemotherapy, which although it has decent response rates has incredibly short durability, perhaps as low as in the range of three months.

Speaker 6: perhaps as low as in the range of three months. So the feedback from the Merkel cell KLO community is that response rate in the range of 15 to 20% and durability as low as four months may be meaningful in this patient population with limited options. Apologies, Chris. Was your question with regards to March 3 or March 2? Not your KLO.

So the feedback from the Merkel cell KOL community is that.

Response rate in the range of 15% to 20% and durability as low as four months.

May be a meaningful in this patient population with limited options apologies Craig was your question with regards to the mantra three year mantra too.

Not yet accounts.

Sorry about that correct.

Alright.

Speaker 4: For mantra two, you know, I think we don't fully know what the FDA would consider approvable for an agnostic indication. There's only been three to date, intractineb, lerotractineb, and pembrolizumab and MSI high patients. I think the feeling is that for patients who have exhausted most other cancer therapies that, you know, a response rate in the range of 40% with durability.

For mantra too I think we don't fully know what the FDA would consider approvable for an agnostic indication. There's only been three to date are <unk>, <unk> and <unk> and MSI high patients.

I think the feeling is that for patients who have exhausted most of their cancer therapies that response rate in the range of 40% with durability.

Speaker 6: in the range of five to six months would probably be meaningful for patients who've exhausted standard therapies, which is the criteria for our patients. But there aren't a lot of examples to be honest in terms of precedent.

In the range of 5% to six months would probably be meaningful for patients who have exhausted standard of care therapies, which is the criteria for our patients.

But there aren't a lot of examples to be honest.

In terms of a precedent.

Speaker 9: I just wanted to follow up, given the interim read-albie to about 12 months from now, do we expect to most of the response rates or will you be in position at that point given kind of case enrollment have at least early indicators of what durability of response is?

Yes if.

If I could just one quick follow up.

Interim rate, helping to about 12 months from now do we expect them as they see response rates or will you get a position at that point given kind of fits the enrolment has at least early indicators and durability of responses.

Speaker 4: Yes, which would you take that one? Sure, so what we plan to do actually is have a meaningful follow-up. So we can quote not just the response rate of duration and response. The likelihood is that we wait till we have about four months worth of follow-up data so that at least we know those responses are meaningful in terms of clinical durability.

Yes, Richard to take that one sure.

We plan to do actually have a meaningful let follow up.

So we can quote in not just the response rate the duration of response.

The likelihood is that we'll wait till we have about four months with a follow up data so that at least we know those responses are.

Meaningful.

In terms of clinical lab durability.

That's helpful. Thank you.

Thanks, Brian I'm sorry.

Speaker 1: I'm showing no questions at this time. I'd like to turn the call back over to Evan, each for long to use for any closing remarks.

Showing no questions at this time I'd like to turn the call back over to avenues for Lucky for any closing remarks.

Speaker 4: Thank you and thanks to our one for for dialing you today. We look forward to giving you an update on our next quarterly results.

Thank you and thanks to everyone for dialing in today, we look forward to giving you an update on our on our next quarterly results.

Speaker 1: Ladies and gentlemen, this does include today's conference. Thank you all for participating. You may now disconnect. Have a great day.

Thank you ladies and gentlemen, this does conclude today's conference. Thank you all for participating you may now disconnect have a great day.

Q3 2021 Rain Therapeutics Inc Earnings Call

Request a DemoDemo

RAIN

Rain Oncology

Earnings