Q3 2022 Rain Therapeutics Inc Earnings Call

November 10, 2022

[music].

Greetings and welcome to the rain Therapeutics third quarter earnings Conference call. At this time, all participants are in a listen only mode.

A brief question and answer session will follow the formal presentation. If anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad. As a reminder, this conference is being recorded it is now my pleasure to introduce your host Dan Ferry with lifestyle Advisors. Please go ahead.

Thank you operator and good afternoon.

With me today on the phone our oven Asia Lucky Chief Executive Officer of Rain Therapeutics Rob.

Robert Double Chief Scientific Officer.

Richard Bryce Chief Medical Officer.

And also in Cabot's one S V P.

During today's call all the niche will provide an overall business update.

Bob will review the interim mantra to data.

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

Nelson will review the financials.

Before we begin I would like to remind you that statements made during this conference call that are not historical facts are forward looking statements within the meaning of the private Securities Litigation Reform Act of 1985.

These forward looking statements are based upon <unk> current expectations and involve assumptions that may never materialize or made.

Prove to be incorrect.

Actual results could differ materially from those anticipated in such forward looking statements as a result of various risks and uncertainties.

As described in <unk> annual report on Form 10-K for the year ended December 31, 2021, and subsequent filings with the Securities and Exchange Commission.

All forward looking statements made during this conference call are based on management's assumptions and estimates as of today November 10th 2022.

Rain undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after today, except as required by law.

That I'd like to turn the call over to other niche Milwaukee.

<unk> therapeutics.

The niche.

Yeah.

Thank you Dan and thanks to everyone for joining us for our third quarter earnings update the team at <unk> continues to drive forward our lead late stage clinical program.

<unk>, our oral small molecule inhibitor of the P 53, MDM to complex again, you may hear us refer to <unk> as Mueller to be brief.

Were excited to release the early data from Miller from our second study called the <unk>. Two study last week and we look forward to sharing a few additional insights from that trial on today's call.

We will also share updates on our other ongoing and planned trials, including some notable changes to our guidance initially discussed as part of a revised corporate presentation and 8-K filing last week.

We also remind you that we announced a $50 million.

Registered offering last week concurrent with the release of the early mantra to data with this additional capital range Casspi cash position is even stronger now providing a cash runway well into 2025. We are excited to welcome several new large healthcare focused funds to reign as part of that financing.

Let me start with our revised corporate guidance before turning to mantra too.

First and foremost we're getting closer to the release of results from our pivotal mantra trial. The Registrational phase III study of <unk> in patients with specific subtypes of LIFO sarcoma.

We completed enrollment with 175 patients in July of this year and we can now refined our guidance for top line data to the first quarter of 2023 or next quarter from the prior guidance of the first half of 2023.

Second we previously stated our interest to pursue merkel cell carcinoma, and indications <unk> and we're aiming to start a new study theyre called the mantra three study however.

We continue to remain convinced of the opportunity for MGM two inhibition in Merkel cell, we now intend to prioritize other larger market opportunities and our ongoing efforts to be very prudent with cash and personnel management and therefore, we do not intend to pursue the mantra three study.

Our priority is to ensure operational execution and the highest ROI indications for the mill identity and franchise.

In light of those priorities the mantra for trial.

Certainly a priority for rain and we expect to start that trial next quarter. The size of the mantra for target patient population is materially large and we're very excited about the science there therefore.

And therefore youll notice that after <unk> initial indication for Mueller and <unk> sarcoma tumors, which exhibit genetic uniformity and driven by where the initial data existed at the time of licensing the program both of our other near term priority indications represent large market tumor agnostic basket trials, the MDM to amplified mantra.

Study and the CDK into a loss mantra for study.

This is very much consistent with our focus on precision strategy had rain.

Finally, I want to come back to the preliminary insights from the mantra to phase III tumor agnostic trial released last week.

Bob will comment in more detail shortly but let me first provide our high level views.

We noticed clear monotherapy activity with two early unconfirmed partial responses and two other patients with early tumor regressions nearing the PR threshold in a study that was the first to evaluate MDM two amplification as a patient selection strategy. We have already been several observations from this study.

Including first.

Safety is thus far been consistent with the prior phase one study and recall a major reason for our licensing of this program was because we felt MELA possessed an optimized dosing schedule that we meaningfully improve its therapeutic index to enable to use as a single agent and in future combinations with various other agents. This.

Is how we intend to grow the value of this franchise there were no surprise findings to us from the early mantra to safety.

Second we are starting to receive some early insight on tumor kinetics with the MDM to protein protein interaction inhibitors. There was more unclear before we anticipated responses might be more gradual with the PPI versus what we've historically seen for the Teekay I class time will tell if we can identify a pattern.

Between early responders versus patients that may take a longer time to achieve a response.

And lastly, <unk> two inhibition with no debt Matan appeared to show initial activity both in patients with other genetic alterations and in patients with a significant number of prior therapies.

These were all very encouraging early observations from mantra to.

Again, we remain very excited about the continued progress of our military <unk> program and are looking forward to the phase III pivotal data from ULA and local sarcoma next quarter.

With that I'd like to turn it over to our President and Chief Scientific Officer, Dr. Bob <unk> Bob.

Thanks <unk>.

Continue the discussion of the mantra to data.

Andre two study continues to enroll patients with MDM to amplified P 53, well type solid tumors with 10 active sites in the U S. Currently we anticipate enrolling a total of approximately 65 patients across a range of solid tumors using the same dosing regimen as in the Registrational mantra trial.

That is with melody Amazon does the 260 milligram and the.

Three out of 14 days schedule.

Regarding patient collection by tumor MDM to copy number the protocol allows enrollment and dosing of patients with Mds <unk> copy number 12 or greater based on local NGF.

And then retroactive central testing using the template platform.

As was anticipated and built into the protocol and analysis plan. There are modest discrepancies between local and central NGF testing with regard to <unk>, resulting in a small number of patients enroll island tumors that had MDM to copy number of less than 12 when potentially tested.

We observed preliminary activity in tumors with less than copy number 12 and greater than copy number eight.

For efficacy assessment at this interim analysis rain only included patients defined as MGM, two amplified using tempus criteria of copy number of greater than or equal to eight and excluded patients with copy number lessening.

Going forward patients will be enrolled based on local MDM to copy number eight versus 12.

As of the cutoff date of October 20, <unk> 2022, the mantra two basket study in melanoma, Montana <unk> amplified patient has enrolled a total of 17 patients.

Are those enrolled 15 patients that started treatment with no damage pattern. In these 15 patients comprised of current safety cohort.

Of the 15 patients dosed Pan have MDM to copy number of eight O greater and are considered evaluable for efficacy of the <unk> patients non evaluable one patient had not yet reached the first scan but is currently continuing on therapy to patients withdrew for reasons unrelated to study drug and two patients were deemed non eligible by central.

Testing criteria.

As of the data cutoff, there are eight patients continuing on therapy, including three who have not reached their first scan of.

Of the 10 efficacy evaluable patients tumor types included but were not limited to lung breast biliary and pancreatic cancers.

Notably every resist evaluable patients had a different tumor histology and nearly every patient had evidence of a coexist an oncogenic driver or tumor suppressor mutation.

As a reminder, the benchmark we set out the tap towards the 30% objective response rate. We are pleased to report that we observed two unconfirmed partial responses and two near partial responses.

Ah patients with pancreatic cancer in a K Ras mutation achieved a partial response with their first scan and has a weighted in their second scan a lung adenocarcinoma patient with an egfr exon 19 deletion as well as a K Ras mutation also achieved a PR at their first scan, but sadly died after this initial assessment due to COVID-19.

In addition to these responses, we observed tumor regressions of 29% on a patient with Cholangiocarcinoma and then <unk> two mutation and a 27% reduction in a patient with breast cancer harboring <unk> kinase mutation.

All the patients with a PR or near PR with the exception of the patient's disease due to COVID-19 are continuing on therapy.

Of the eight patients still ongoing therapy. The longest patient continues on study for over nine months.

Safety was reported and 15 Evaluable patients those who received at least one dose in all of them on time and is consistent with what was reported in the prior phase one study had met with Allentown.

The 260 milligram dose of <unk> administered three out of every 14 days was chosen from the phase one study based both on the ability to achieve a higher dose and off hire C. Max as well as reduce toxicity, especially with respect to the on target hematologic toxicities such as thrombocytopenia.

No new safety signals were observed and the toxicity profile on frequencies are completely consistent with prior experience at this dose and schedule.

Notably patients in the safety Evaluable set experienced four median prior lines of therapy with a range of 1% to 11 prior therapies. The pancreatic patient responder had four prior therapies the lung cancer responder fixed prior therapies in a breast cancer patient with a narrow response five prior therapies.

To reiterate <unk> point made above we view. These early data is encouraging with respect about anti tumor activity and safety, particularly in this histologically and genetically diverse set of patients.

At this point I will hand, it over to our Chief Medical Officer, Richard Bryce to discuss additional updates around range clinical trial pipeline.

Sure.

Thank you Bob and good afternoon, everyone.

Moving on to our pivotal phase III <unk> study, we previously announced that we have completed enrollment of 175 patients at the end of July five months ahead of our prior year end 2022 guidance.

In fact, the trial began as the first clinical site in July 2021, and therefore enrolled in about 12 months.

We believe the accelerated enrollment completion speaks to the tremendous unmet need in patients with Dedifferentiated lipo sarcoma for which <unk> offers a targeted therapeutic strategy relative to standard cytotoxic options.

We now anticipate top line data in the first quarter of 2023 towards the early half of the previous guidance as the first half of 2023.

As a reminder, we met with the FDA and EMA prior to the startup of Memphis study and therefore, we anticipate that if demand for data are supportive we will submit an NDA for millet, Amazon Indeed difference that you'd like us to come in.

In the United States with similar submissions in Europe , and possibly other regions as well.

We expect shortly to start a second tumor agnostic basket study manager for which will be a phase one stroke. Two trial designed to enroll 30 patients with wild type P. 53 advanced solid tumors that also exhibit loss of the CDK <unk> E <unk>.

This trial will be our first combination regimen with <unk> using a checkpoint inhibitor Roche has to centric <unk> Matt.

As a reminder, lots of the gene CDK in today and as protein product <unk> off.

Leads to increased MDM two levels.

<unk> is a natural regulator of MDM too and helped to maintain P 53 function in cancer cells.

There are a significant number of patients with wildfire P 53 solid tumors with advanced disease.

But lots of CDK <unk> and.

In fact this is the second most common tumor suppressor operation after <unk>, three mutation occurring and as many as 6% to 7% or more of all solid tumors, representing over 45000 patients per year in the United States.

The mansion full study is anticipated to start next quarter.

And finally as <unk> mentioned, we have decided to prioritize merkel cell carcinoma, as an indication familial <unk>.

And therefore have discontinued planning for the Master II trial.

As a small and lean biotechnology organization, we are electing to focus our financial resources and the time of our clinical team on indications that represent a greater value to the overall <unk> franchise as.

As well as allowing us the ability to ensure timely and successful execution of our clinical strategy.

With multiple clinical strategies <unk> underway, we are excited by all the emerging and potential new clinical data and the associated potential commercialization opportunities and benefits to patients while providing a best in class <unk> inhibitor for patients across multiple genotypes.

<unk>.

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

Awesome.

Thank you Richard and good afternoon, everyone I am pleased to provide an update to our financial results for the third quarter ended September 32022.

I would also like to invite you to review our Form 10-Q filed today for more details.

For the third quarter of 2022, we reported a net loss of $18 million compared to a net loss of $18 4 million in the third quarter of 2021.

Research and development expenses of $14 5 million in the third quarter of 2022 were slightly lower as compared to $15 3 million in the third quarter of 2021.

Decrease was primarily achieved the milestone fee to date, you think youll have $5 5 million incurred in the third quarter of 2021, partially offset by higher external R&D costs for <unk> as well as higher payroll related costs for R&D personnel.

General and administrative expenses of $3 9 million in the third quarter of 2022 were slightly higher as compared to $3 2 million in the same quarter of 2021.

The increase was primarily due to higher payroll related costs for our G&A personnel outside consulting legal cost and payers third party G&A cost.

As of September 32022, Grand continues to have a strong balance sheet with $90 7 million in cash cash equivalents and short term investments.

As announced last week, we completed a 50 million registered offering of common stock, which increases our pro forma cash balance to over $140 million and provides additional runway well into 2025 with that I'll now turn the call back over to <unk>.

Thanks Nelson.

Now I'll be happy to answer any questions operator.

Thank you we will now be conducting a question and answer session.

I would like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue. You May Press Star two if you would like to remove your question from the queue.

For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Your first question comes from Michael Schmidt with Guggenheim. Please go ahead.

Hey, guys. Thanks for taking my questions.

Just had a couple of follow ups on <unk> two.

One question, maybe for Bob was if you could talk a bit more about the <unk> amplification.

And I think you said you have seen activity below 12 copy number and yes.

Maybe if you could talk about which patients.

In this study that did have activity with the lower cut off when all you should think about the overall market size, perhaps going forward with the eight.

But the age cut off.

Yeah.

Thanks for the question Michael Bob Yes, Thanks for the question.

Maybe I'll start with the last part first so we're anticipating that the market size is approximately 8000 patients per year.

As you as you said, we message that we've dropped the copy number from 12 to eight based on activity that we've seen.

In that range.

We haven't released details on individual patients and what their copy number was but obviously we're seeing activity.

Matt copy numbers lower than the initial threshold, which has prompted a re analysis on many levels and the decision to drop that copy number.

We've always said that we don't think that there'll be a significant <unk>.

<unk> shipped between very high copy number and sensitivity versus lower copy number we think that there will be a threshold effect.

And I think thats.

Adjustment to the protocol going forward reflects what we're seeing in real time with the study.

Yes.

Okay great.

Question on the data obviously that.

Our management team so far enrolled.

Our broad diversity of cancer types in the study, but I thought it was interesting that there were a fair amount of Commutations of car NK rise and so let's.

But just wondering if you could share your thoughts on.

Whether whether the drug is perhaps more active in certain types of cancers, and how you think about the impact of these potential call mutations.

Yes, thanks for that question.

We've obviously been very interested in the question of co mutations.

Previously published.

Co mutation status.

With oncogenic drivers at ACR earlier this year. So we have some data on that we expect a roughly somewhere between 15 and 20% of all patients with MDM too.

Amplification will have.

Co mutation our belief has always been that these are an independent pathways and may not significantly impact.

The effect of Miller, Demeton, which obviously is affecting the.

<unk> P 53 pathway rather than for example, RAF switches in the RT K Ras RAF map kinase pathway.

We obviously.

If you think about kind of the reverse situation patient.

Patients with oncogenic drivers such as Egfr about half the time half of P 53 mutation and while there are some long term prognostic impacts of that we obviously still get there.

Those targeted therapies.

For the Egfr alterations, despite there being P 53, alterations and kind of thinking versus the.

The reverse our inverse situation.

But we are obviously continuing to look at this one we're getting a next generation sequencing comprehensive next generation sequencing on all of our patients. So this allows us to again look in real time at these relationships and try to better understand whether there might be future impacts that we have not yet anticipated.

Sure.

Great well, thank you and congrats on the data.

Thanks, Michael.

Next question comes from Yigal <unk> with Citi. Please go ahead.

Yeah, Hi, I'm finished and Bob and team. Thanks for taking the question just to see it for me.

With respect to the decision to stop the mantra three can you just say approximately what the cost savings will be on that on that decision and then with respect to the choice to lower the cut off do copy number eight.

Does that make a meaningful difference to the long term market opportunity.

The drug thank you.

Thanks for the question Yigal ill take the first question.

As Bob to address the second question in terms of what the copy number change and go to the market opportunity in terms of the module.

<unk> study.

In terms of the cost savings, we can assume it's probably less than a quarter's worth of cash in terms of our historical burn rate. So hopefully that provides you. Some some sort of read through in terms of the extension of that gives us by itself.

And for the second part of the question the anticipated increase in market is.

Little above 40%.

Increase the market size by dropping the copy number.

Okay, Great and then just one follow up which is more strategic in nature and long term, but obviously you guys are aware that the orange or starting a phase III in first line.

D differentiator Vipers, Oklahoma soon.

Obviously, you guys are doing second line, but to what extent have you thought about the potential to do a first line trial down down the road yet.

Yes, I can I can take that when you got things for that so I think it's important to be specific in terms of what first line means as it as it is distinguished from treatment naive patients.

So what we think happens in the treatment landscape and as part of the standard protocol for LIFO sarcoma patients with differentiated subtypes, we do expect some patients to receive.

Anthracycline around the time of surgery, as adjuvant or new adjuvant care, so we'd like to remind everybody that in the mantra trial designed patients may receive <unk> as the first line metastatic therapy, if those patients who previously received an anthracycline around the time of surgery.

So we would anticipate that if our trial is successful.

We would achieve a label, possibly in line with the trial design of the mantra trials in.

In first line and beyond metastatic patients. So I just wanted to clarify that as we talked about first line versus treatment naive.

In terms of subsequent strategies for LIFO sarcoma, if the mantra study is successful I think there's quite a few opportunities to expand the reach of <unk>, but I don't think we necessarily want to talk about it.

See what the mantra data shows us I hope I hope that's helpful.

Yeah. Thank you very much.

Next question comes from Jeff Jonas with Oppenheimer. Please go ahead.

Can you hear me.

Yes, Hi, Jeff.

Hi, Avinash.

I appreciate you taking the question I just wanted to see any guidance on timing of ramp.

The enrollment on defaults in our basket trial, given you're at 25% now or around 25% now.

Just whats your thoughts are as far as timing to the next data update or full topline data and then the second question was around.

<unk>.

<unk> observed in the basket trial, and whether you are allowed.

Odyssey of medications.

The trial at this stage.

Thanks, Jeff I'll take the first question ask Richard to comment on the safety and the safety question.

We're not going to provide any additional guidance at the current time, Jeff in terms of subsequent milestones for the mantra <unk> study. So sorry, we can't we can't be more descript there but.

But nothing nothing additional.

Our mantra to guidance.

We talked about.

Sure so the.

The AE profile that we've observed and we published or presented is pretty much identical to what's been shared before with the.

Phase one Daiichi Sankyo study that you went to one study that study that will be published shortly in that in <unk>.

So we're very happy with that and very pleased with the consistency question regarding anti nausea agents on team ethics Theres not mandated in the basket study, it's at the physician's discretion entirely at the physician's discretion.

Yeah.

Great I appreciate that thank you.

Thanks, Jeff.

Once again, if you would like to ask a question. Please press star one on your telephone keypad.

Your next question comes from Mitchell Kapoor with H C. Wainwright. Please go ahead.

Hi, everyone. Thanks for taking the questions and congrats on the recent data.

The first question. We have is what kind of analysis could we see in the top line phase III lbs data do you have any details on how many patients about we could see or any other details about that readout and then if data are positive how soon could you file for regulatory approval and potentially be on the market.

Hi, Michel and thanks for the question. So let me let me take that first question.

So we're not going to do what I can provide that kind of detail in terms of what we're going to say in terms of what we.

What data is going to be included in the top line.

News release.

And I think in terms of the timelines to potentially filing.

<unk> approval.

I can provide that specific guidance at this point other than saying that we expect it to be within conventional timelines post the phase III.

So we don't expect.

Anything materially to delay that process if the if the market are supportive so other than that were not completed any additional clarity Mitchell.

Yes, no problem and then I.

I guess just on the benchmarks for the data would you be able to share kind of what what would be considered positive on PFS and should we also be looking at response rates to some degree.

Yes. So so no to response rates, we said before that micro sarcomas tend to not respond to essentially any therapy with very modest.

Single digit response rates to a variety of regimens that have historically been tried in this patient population. So response rate is not an adequate measure of efficacy and as soon as population.

As a reminder, we designed the mantra study.

Based on an assumption of a doubling of progression free survival from the standard of care Trabecular <unk>. We think if that is achieved that is a.

Very clinically meaningful benefit.

Especially in light of the AE profile that goes with <unk> versus the conventional therapies. So we think as designed achieving that primary endpoint with the W. PFS would be it would be rather substantial.

And really.

Largely agreed by by many of the Kols in the space as well.

Great. Thank you for taking the questions.

Thank you.

Next question Sumit Roy with Jones Research. Please go ahead.

Hi, everyone. Congratulations on all the progress in the data.

My apologies I missed the top part of the call. So if you've answered this already but curious if youre going to put out.

In the basket from the basket trial, the Spider plot.

All of these patients how rapid is that tumor the rate of reduction and do you see deepening of response with time or they kind of flatten out after the initial drop in the tumor sites.

I assume.

Let me turn it over to Bob.

Thanks for the question, it's an interesting one we don't yet.

I guess the.

The short answer is we don't yet know enough about whether thats protein protein interaction disruptor no damage.

We will have similar kinetics to for example, <unk>.

In terms of rapid responses and we have seen some responses and anti tumor activity on the first scan we have seen some deepening but I think it's still too early to understand the kind of average kinetics of response for this drug in this type of mechanism.

Are you planning to put out the Spider plots later on the more mature update.

We could assume that we haven't we haven't declared our intent is to what data we're going to put out win.

But I think it's important to mention that in the <unk>.

Swim Lane plot that we did include in our corporate presentation and did release.

Given that many of the comments that we've included in the press release around.

Some of those early responders and the timing associated with those responses.

Tumors plot I think you can kind of back into what it preliminary spider pumps can look like.

As we did mentioned that both the early responders did respond in the first scan.

I think we do highlight how long have you been on study so well.

I'll leave it at that but we don't want to be more descript here incremental to what's already been released.

Certainly thank you for taking my questions and congratulations again.

Thanks, Jim.

There are no further questions I would like to turn the floor over to <unk> for closing remarks.

Thank you operator, we look forward to updating everyone on our year end 2022 call next and I want to thank everyone for joining us today.

This concludes today's teleconference. You may disconnect your lines at this time and thank you for your participation.

Yeah.

Goodbye.

[music].

Greetings and welcome to the rain Therapeutics third quarter earnings Conference call. At this time, all participants are in a listen only mode.

Thank you operator and good afternoon.

With me today on the phone our oven Asia, Lunky, Chief Executive Officer of Rain Therapeutics Rob.

Robert Double Chief Scientific Officer.

Richard Bryce Chief Medical Officer.

And also in Cabot's one SVP.

Let's turn.

During today's call all the niche will provide an overall business update.

Bob will review the interim mantra to data Richard will provide an update on <unk> clinical programs.

And Nelson will review the financials.

These forward looking statements are based upon <unk> current expectations and involve assumptions that may never materialize.

<unk> proved to be incorrect.

Actual results could differ materially from those anticipated in such forward looking statements as a result of various risks and uncertainties as described in <unk> annual report on Form 10-K for the year ended December 31, 2021, and subsequent filings with the Securities and Exchange Commission.

All forward looking statements made during this conference call are based on management's assumptions and estimates as of today November 10 2022.

Rain undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after today, except as required by law.

With that I'd like to turn the call over to other niche Milwaukee CEO of <unk> therapeutics of an issue.

Thank you Dan and thanks to everyone for joining us for our third quarter earnings update the team at <unk> continues to drive forward our lead late stage clinical program.

<unk>, our oral small molecule inhibitor of the P 53, MDM to complex again, you may hear us refer to <unk> as Mueller to be brief.

We were excited to release the early data from <unk> from our second study called the mantra to study last week and we look forward to sharing a few additional insights from that trial on today's call. We will also share updates on our other ongoing and planned Mueller trials, including some notable changes to our guidance initially discussed as part of our revised corporate.

Presentation, and 8-K filing last week.

We also remind you that we announced a 50 million.

Registered offering last week concurrent with the release of the early March of two data with this additional capital range caspase cash position is even stronger now providing a cash runway well into 2025. We are excited to welcome several new large healthcare focused funds to reign as part of that financing.

Let me start with our revised corporate guidance before turning to monitor too.

First and foremost we're getting closer to the release of results from our pivotal mantra trial. The Registrational phase III study of Mila in patients with specific subtypes of LIFO sarcoma.

Second we previously stated our interest to pursue Merkel cell carcinoma is an indication with <unk> and we're aiming to start a new study there called the mantra three study however.

Our priority is to ensure operational execution and the highest ROI indications for the <unk> franchise.

In light of those priorities the mantra for trial.

Certainly a priority for rain and we expect to start that trial next quarter. The size of the mantra for target patient population is materially large and we're very excited about the science there.

Therefore, you will notice that after raise initial indication for Mueller and LIFO sarcoma tumors, which exhibited genetic uniformity and driven by where the initial data existed at the time of licensing program. Both of our other near term priority indications represent large market tumor agnostic basket trials, the MDM to amplified mantra.

<unk> study and the CDK into a loss mantra for study.

This is very much consistent with our focus on our precision strategy had rain.

Finally, I want to come back to the preliminary insights from the mantra to phase III tumor agnostic trial released last week, Bob will comment in more detail shortly but let me first provide our high level views.

We noted clear monotherapy activity with two early unconfirmed partial responses and two other patients with early tumor regressions nearing the PR threshold.

A study that was the first to evaluate MGM two amplification as a patient selection strategy.

Already been several observations from this study, including first safety has thus far been consistent with the prior phase one study and recall a major reason for our licensing of this program was because we felt <unk> possessed and optimize dosing schedule to be meaningfully improve its therapeutic index to.

It's used as a single agent and in future combinations with various other agents.

This is how we intend to grow the value of this franchise. There were no surprise findings to us from the early mantra to safety.

Second we are starting to receive some early insight on tumor kinetics with the MDM to protein protein interaction inhibitors. There was more unclear before we anticipated responses might be more gradual with the PPI versus what we've historically seen for the Teekay High class time will tell if we can identify a pattern.

Early responders versus patients that may take a longer time to achieve a response.

And lastly, <unk> two inhibition with <unk> appeared to show initial activity both in patients with other genetic call durations and in patients with a significant number of prior therapies.

These were all very encouraging early observations from mantra too.

At <unk>, we remain very excited about the continued progress of our <unk> program and are looking forward to the phase III pivotal data from ULA and LIBOR sarcoma next quarter.

With that I'd like to turn it over to our President and Chief Scientific Officer, Dr. Bob <unk> Bob.

Thanks, <unk>, let's continue the discussion of the mantra to data.

I'm Andre two study continues to enroll patients with MDM to amplified P 53, wild type solid tumors with 10 active sites in the U S. Currently we anticipate enrolling a total of approximately 65 patients across a range of solid tumors.

Same dosing regimen as in the Registrational mantra trial.

That is with millet Amazon does the 260 milligram and the three out of 14 day schedule.

Regarding patient selection by tumor MDM to copy number the protocol allows enrollment and dosing of patients with MDM to copy number 12 or greater based on local NGF.

And then retroactive central testing using the template platform.

As was anticipated and built into the protocol and analysis plan. There are modest discrepancies between local and central NGF test in with regard to nvme, two resulting in a small number of patients enrollment tumors that had MDM to copy number of less than 12 when centrally tested.

We observed preliminary activity in tumors with less than copy number 12 and greater than copy number eight.

For efficacy assessment at this interim analysis rain only included patients defined as MDM to amplified using the tempus criteria of copy number greater than or equal to eight and excluded patients with copy number less than eight.

Going forward patients will be enrolled based on local MDM to copy number eight versus 12.

As of the cutoff date of October 26, 2022, the module two basket study in melanoma tenant <unk> amplified patient has enrolled a total of 17 patients.

Of those enrolled 15 patients have started treatment with no damage pattern in these 15 patients comprise the current safety cohort.

Of the 15 patients dosed Pan have MDM to copy number of Ido greater and are considered evaluable for efficacy of the five patients not a valuable one patient had not yet reached the first Gan, but is currently continuing on therapy to patients withdrew for reasons unrelated to study drug and two patients were deemed non eligible by.

Testing criteria.

As of the data cutoff, there are eight patients continuing on therapy, including three who have not reached their first scan.

Of the 10 efficacy evaluable patients tumor types included but were not limited to lung breast biliary and pancreatic cancers.

Notably every resist evaluable patients had a different tumor histology and nearly every patient had evidence of a coexisting oncogenic driver or tumor suppressor mutation.

As a reminder, the benchmark we set out the tab towards a 30% objective response rate. We are pleased to report that we observed two unconfirmed partial responses and two near partial responses.

A patient with pancreatic cancer in a K Ras mutation achieved a partial response with our first scan and is awaiting their second scan a lung adenocarcinoma patient with an egfr exon 19 deletion as well as a K Ras mutation also achieved a PR at their first scan, but sadly died after this initial assessment due to COVID-19.

In addition to these responses, we observed tumor regressions of 29% on a patient with Cholangiocarcinoma and an <unk> two mutation and a 27% reduction in a patient with breast cancer harboring <unk> kinase mutations.

All the patients with a PR or near PR with the exception of the patient's disease due to COVID-19 are continuing on therapy.

Of the eight patients still ongoing therapy. The longest patient continues on study for over nine months.

Safety was reported 15 evaluable patients those who received at least one dose in all of downtown and is consistent with what was reported in the prior phase one study of <unk>.

The 260 milligram dose of <unk> administered three out of every 14 days was chosen from the phase one study based both on the ability to achieve a higher dose and thus higher <unk> as well as reduced toxicity, especially with respect to the on target hematologic toxicities such as thrombocytopenia.

No new safety signals were observed and the toxicity profile on frequencies are completely consistent with prior experience at this dose and schedule.

Notably patients for the safety Evaluable <unk> experienced four median prior lines of therapy with a range of 1% to 11 prior therapies. The pancreatic patient responder had four prior therapies the lung cancer, a responder fixed prior therapies in a breast cancer patient with a narrow response five prior therapies.

At this point I will hand, it over to our Chief Medical Officer, Richard Bryce to discuss additional updates around range clinical trial pipeline.

Sure.

Thank you Bob and good afternoon, everyone.

Moving on to our pivotal phase III <unk> study, we previously announced that we have completed enrollment of 175 patients at the end of July five months ahead of our prior year end 2022 guidance.

In fact, the trial began as the first clinical site in July 2021, and therefore enrolled in about 12 months.

We believe the accelerated enrollment completion speaks to the tremendous unmet need in patients with Dedifferentiated lipo sarcoma for which Miller Demeton officer targeted therapeutic strategy relative to standard cytotoxic options.

We now anticipate top line data in the first quarter of 2023 toward the early half of the previous guidance. The first half of 2023.

As a reminder, we met with the FDA and EMA prior to the start with the mattress study and therefore, we anticipate that if the mantra data are supportive we will submit an NDA for <unk> indeed differentiated licenses.

In the United States with similar submissions in Europe , and possibly other regions as well.

This trial will be our first combination regimen with <unk> using a checkpoint inhibitor rushes to centric or a Tesla GMAT.

As a reminder, lots of the gene CDK in today and as protein product <unk> 14 or <unk>.

Leads to increased MDM two levels.

<unk> is a natural regulator of MDM too and helped to maintain P 53 function in cancer cells.

There are a significant number of patients with wildfire P 53 solid tumors with advanced disease.

Little bit loss of CDK and.

In fact this is the second most common tumor suppressor operation after P 53, mutations occurring and as many as 6% to 7% or more of all solid tumors, representing over 45000 patients per year in the United States.

The mansion full study is anticipated to start next quarter.

And finally as <unk> mentioned, we have decided to de prioritize merkel cell carcinoma, as an indication familiar of MSR.

And therefore have discontinued planning for the Master II trial.

As well as allowing us the ability to ensure timely and successful execution of our clinical strategy.

With multiple clinical strategies similar demonstrate underway. We are excited by all the emerging and potential new clinical data and the associated potential commercialization opportunities and benefits to patients while providing a best in class <unk> inhibitor for patients across multiple genotypes.

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

Nelson.

Thank you Richard and good afternoon, everyone.

I'm pleased to provide an update to our financial results for the third quarter ended September 32022.

I would also like to invite you to review our Form 10-Q filed today for more details.

For the third quarter of 2022 were reported a net loss of $18 million compared to a net loss of $18 4 million in the third quarter of 2021.

Research and development expenses of $14 5 million in the third quarter of 2022 were slightly lower as compared to $15 3 million in the third quarter of 2021.

The decrease was primarily due to the milestone fee. Today do you think you have $5 5 million incurred in the third quarter of 2021.

Sally upset by higher external R&D costs for <unk>.

As higher payroll related costs for R&D personnel.

General and administrative expenses of $3 9 million in the third quarter of 2022 were slightly higher as compared to $3 2 million in the same quarter of 2021.

The increase was primarily due to higher payroll related costs for our G&A personnel outside consulting legal cost and payers third party G&A cost.

As of September 32022, Grand continues to have a strong balance sheet with $90 7 million in cash cash equivalents and short term investments.

Thanks Nelson.

I will be happy to answer any questions operator.

Thank you we will now be conducting a question and answer session.

For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Your first question comes from Michael Schmidt with Guggenheim. Please go ahead.

Hey, guys. Thanks for taking my questions.

I just had a couple of follow ups on <unk>.

One question, maybe for Bob was if you could talk a bit more about the <unk> amplification.

And I think you said you have seen activity below 12 copy number.

Maybe if you could talk about which patients.

In this study that did have activity with the lower cutoff then all you should think about.

The overall market size, perhaps going forward with the eight.

Eight cutoffs.

Thanks for the question Michael Yes.

Yes, thanks for the question.

Maybe I'll start with the last part first so we're anticipating that the market size is approximately 8000 patients per year.

As you as you said, we message that we've dropped the copy number from 12 to eight based on activity that we've seen.

In that range.

We haven't released details on individual patients and what their copy number was but obviously, we're seeing activity at.

That copy numbers lower than the initial threshold, which has prompted a re analysis on many levels and the decision to drop that copy number.

We've always said that we don't think that there'll be.

Significant.

Our relationship between very high copy number and sensitivity versus lower copy number we think that there will be a threshold effect.

I think thats.

The adjustment to the protocol going forward reflects what we're seeing in real time with the study.

Okay great.

Follow up question on the data obviously that.

Our management team so far enrolled.

Broad diversity of cancer types in this study, but I thought it was interesting that there were a fair amount of call mutations occurring including K rather than sell.

But just wondering if you could share your thoughts on.

Whether whether the drug is perhaps more active in certain types of cancers, and how you think about the impact of these potential call mutations.

Yes, thanks for that question.

We've obviously been very interested in the question of co mutations.

We've previously published.

Co mutation status.

With oncogenic drivers at ACR earlier this year. So we have some data on that we expect the roughly somewhere between 15 and 20% of all patients with MDM too.

Amplification will have co mutation.

Our belief has always been that these are an independent pathways and may not significantly impact.

The effect of Miller, Demeton, which obviously is affecting the <unk>.

<unk> P 53 pathway rather than for example, RAF switches in the RT K Ras RAF map kinase pathway.

We obviously.

If you think about kind of the reverse situation.

Patients with oncogenic drivers such as Egfr about half the time have a P 53 mutation and while there are some long term prognostic impacts of that we obviously still get those targeted therapies.

For the Egfr alterations, despite there being P 53, alterations and kind of thinking.

The reverse our inverse situation.

But we are obviously continuing to look at this and we're getting a next generation sequencing comprehensive next generation sequencing on all of our patients. So this allows us to again look in real time at these relationships and try to better understand whether there might be future impacts that we have not yet anticipated.

Sure.

Great well, thank you and congrats on the data.

Thanks, Michael.

Question comes from <unk> <unk> with Citi. Please go ahead.

Yeah, Hi, avenues, and Bob and team Thanks for taking the question.

The seed for me.

Right.

Does that make a meaningful difference to the long term market opportunity for the drug. Thank you.

Thanks for the question Yigal ill take the first question on all asked Bob to address the second question in terms of what the copy number change to the market opportunity in terms of the mantra three study.

And you would offer the second part of the question.

<unk> increase in market is.

A little above 40%.

Increase in the market size by dropping the copy number.

Okay, Great and then just one follow up which is more strategic in nature and long term, but obviously you guys are aware that boehringer is starting.

The phase III in first line.

D differentiator Vipers, Oklahoma soon.

Obviously, you guys are doing second line, but to what extent have you thought about the potential to do a first line trial down down the road yet.

Yes, I can I can take that when you got it. Thanks for that so I think it's important here to be specific in terms of what first line means as it as it is distinguished from treatment naive patients.

So what we think happens in the treatment landscape and as part of the standard protocol for LIFO sarcoma patients with differentiated subtypes, we do expect some patients to receive.

Anthracycline around the time of surgery as adjuvant Neo adjuvant care, so we'd like to remind everybody that in the mantra trial designed patients may receive <unk> as the first line metastatic therapy, if those patients who previously received an anthracycline around the time of surgery.

So we would anticipate that if our trial is successful.

We would achieve a label, possibly in line with the trial design of the mantra trials in.

In first line and beyond metastatic patients. So I just wanted to clarify that as we talked about first line versus treatment naive.

See what the mantra data shows us hope I hope that's helpful.

Yes, thank you very much.

Next question comes from Jeff Jones with Oppenheimer. Please go ahead.

Thanks, guys can you hear me.

Hi, Jeff.

Hi, Avinash.

I appreciate you taking the question I just wanted to see any guidance on timing of ramp.

The enrollment on defaults in our basket trial, given you're at 25% now or around 25% now.

Just whats your thoughts are as far as timing to the next data update or full topline data and then the second question was around.

<unk>.

<unk> observed and the basket trial and whether you are allowed.

Obviously your medications in the trial at this stage. Thanks.

Thanks, Jeff I'll take the first question and ask Richard to Covenant on the safety and the safety question.

We're not going to provide any additional guidance at the current time, Jeff in terms of subsequent milestones for the mantra to study. So so sorry, we can't we can't be more descript there but.

But nothing nothing additional.

Our mantra to guidance.

We've talked about.

Sure. So the AE profile that we've observed and we published or presented is pretty much identical to what's been shared before with the phased.

Phase one Daiichi Sankyo study that you want to study that study that will be published shortly in that in <unk>.

So we're very happy with that and very pleased with the consistency question regarding anti nausea agents on team ethics. This is not mandated in the basket study, it's at the physician's discretion entirely at the physician's discretion.

Great I appreciate that thank you.

Thanks, Jeff.

Once again, if you would like to ask a question. Please press star one on your telephone keypad.

Your next question comes from Mitchell Kapoor with H C. Wainwright. Please go ahead.

Hi, everyone. Thanks for taking the questions and congrats on the recent data.

Hi, Michel Thanks for the question. So let me let me take that first question.

So we're not going to do we're not going provide didn't kind of detail in terms of what we're going to say in terms of what we.

What data is going to be included in the top line.

News release.

And I think in terms of the timeline to potentially filing.

Geo toward approval.

I can provide that specific guidance at this point other than saying that we expect it to be within conventional timelines post the phase III.

So we don't expect.

Anything materially to delay that process if the if the mantra data are supportive so other than that we are not can provide any additional clarity Mitchell.

Yes, no problem and then.

I guess just on the benchmarks for the data would you be able to share kind of what what would be considered positive on PFS and should we also be looking at response rates to some degree.

Yeah. So no to response rates, we said before that Mike will start comas tend to not respond to essentially any therapy was very modest.

Single digit response rates to a variety of regimens that have historically been tried in this patient population. So response rate is not an adequate measure of efficacy in this population.

As a reminder, we designed the mantra study.

Just on an assumption of a doubling of progression free survival from the standard of care Trabecular <unk>. We think if that is achieved that is.

Very clinically meaningful benefit.

Especially in light of the AE profile that goes with no <unk> versus the conventional therapies. So we think as designed achieving that primary endpoint with a double your PFS would be it would be rather substantial.

And really.

Largely agreed by by many of the Kols in the space as well.

Great. Thank you for taking the questions.

Thank you.

Next question Sumit Roy with Jones Research. Please go ahead.

Hi, everyone. Congratulations on all the progress in the data.

My apologies I missed the top part of the call. So if you've answered this already but curious if youre going to put out.

In the basket from Nebraska tumor trial, the Spider plot of.

These patients how rapid is the tumor the rate of reduction and do you see deepening of response with time or they kind of flatten out after the initial drop in the tumor sites.

I assume it.

Actually let me turn it over to Bob.

Thanks for the question, it's an interesting one we don't yet.

I guess the.

The short answer is we don't yet know enough about whether thats protein protein interaction disruptor no damage.

We will have similar kinetics to for example, <unk>.

Are you planning to put out the Spider plots later on the more mature update.

We could see which we haven't we haven't declared our intent is to what data we're going to put out win.

But I think it's important to mention that in these.

Swim Lane plot that we didn't include in our corporate presentation and did release.

Given that many of the comments that we've included in the press release around.

Some of those early responders and the timing associated with those responses.

<unk> plant I think you can kind of back into what it preliminary spider plants kind of look like.

As we did mentioned that in both the early responders did respond in the first scan.

I think we do highlight how long have you been on study so well.

We'll leave it at that but we don't want to be more descriptive here incremental to what's already been released.

Certainly thank you for taking the questions and congratulations again.

Thanks, Jim.

There are no further questions I would like to turn the floor over to <unk> for closing remarks.

Thank you operator, we look forward to updating everyone on our year end 2022 call next and I want to thank everyone for joining us today.

This concludes today's teleconference. You may disconnect your lines at this time and thank you for your participation.

Q3 2022 Rain Therapeutics Inc Earnings Call

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