Q1 2022 Rain Therapeutics Inc Earnings Call
[music].
Good afternoon, and welcome to the rain Therapeutics first quarter 2022 earnings call. All participants will be in listen only mode should you need assistance. Please signal conference specialist by pressing the sparky followed by zero.
After today's presentation there'll be an opportunity to ask questions.
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Please note. This event is being recorded I would now like to turn the conference over to Bob Yeah. There's a lifestyle advisors. Please go ahead.
Thank you operator.
I mean every one.
With me today on the phone are often H, Milwaukee, Chief Executive officer of rain Therapeutics.
Double Chief Scientific Officer, Richard Bryce, Chief Medical Officer, Nelson, how about two on <unk>.
<unk> VP of finance during today's call <unk> will provide an overall business update.
Richard will provide an update on range clinical programs, Bob will review the research efforts Nelson will review the financials before I begin I'd like to remind you that statements made on this conference call that are not historical facts are forward looking statements within the meaning of the private securities.
Litigation Reform Act of 1095.
These forward looking statements are based upon <unk> current expectations and involve assumptions that may never materialize or may prove to be incorrect actual results could differ materially from those anticipated in such forward looking statements as a result of various risks and uncertainties as described in <unk> annual report on.
Form 10-K for the year ended December 31, 2021, and in subsequent filings with the Securities and Exchange Commission at all.
All forward looking statements made during this conference call are based on management's assumptions and estimates as of today may four 2022 right.
<unk> undertakes no undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after today, except as required by law.
With those prepared remarks, it's my pleasure to turn the call over to over two avenues philosophy.
Oh of rain Avenue.
Thank you Bob and thanks to everyone for joining us for our first quarter earnings call and the most recent quarter and since the end of <unk> year, We continue to advance the mill of dermatology program and progressing nicely with enrollment into the four planned clinical trials with two additional clinical trials planned to start in the fourth quarter of this year.
As a reminder, we may refer to mill of <unk>, <unk> or <unk> 32 on occasion.
The day rate is very much a clinical execution story and were very excited about our progress.
First and foremost our phase III trial, the mantra study for <unk> in patients with LIBOR sarcoma has progressed well and we can now offer guidance on completion of enrollment and refine the availability of topline pivotal phase III data from the mantra study, we anticipate completion of enrollment by the end of this year.
With top line data anticipated in the first half of 2023, which is earlier than previously guided.
Richard will provide more color on our progress.
Based on our updated guidance for the pivotal mantra study and our existing cash balance. We believe there is ample cushion between the availability of pivotal data and our cash runway, which takes us into the first half of 2020 for avoiding the need for additional equity financing ahead of phase III data.
Our expectation is that if the data are supportive of mantra study would enable a regulatory filing for <unk> and <unk> sarcoma in the U S Europe and possibly other regions. As a reminder, the mantra study was designed based on discussions with the FDA and EMA held in early 'twenty one.
Our phase II tumor agnostic mantra to study is also proceeding according to plan and we continue to anticipate an interim data readout on approximately the first 10 patients in the fourth quarter of this year to recap. This trial will evaluate <unk> in a basket trial across approximately 65 patients in the U S.
With solid tumors that exhibit high MDM to gene amplification.
The early data show clinically meaningful responses, our intention would be to approach and regulatory agencies to obtain guidance on an estimated cohort size for purposes of registration from an expanded phase III study rather than pursuing a separate phase III study.
The prior quarter, we stated that we would start the additional two studies for <unk> in the second half of this year pending appropriate progress in enrollment of the first two studies. The reason for getting the studies was to ensure appropriate use of cash resources at the company until avoid triggering additional expense there were any material budgetary.
Concerns based on enrollment of the first two studies.
We confirm that we now will take to start both studies in the fourth quarter of this year.
This includes the phase II mantra three study in Merkel cell carcinoma, evaluating poly AUM of virus positive patients, who are resistant or refractory to checkpoint inhibitor therapy.
And phase <unk> mantra for study evaluating the combination of <unk> with a checkpoint inhibitor, Russia has the lithium app and a basket study in patients with P. 53, Wild type advanced solid tumors exhibit loss of the gene CDK and two way.
Richard will provide more detail on the module three and mantra for planned studies shortly.
Coming back to our cash position, we continue to anticipate that based on the progress of our ongoing studies.
Ample cash one way beyond our phase III data from the mantra study and we anticipate to be able to complete all four studies within the articulated cash runway into the first half of 2024.
Continue to progress our early research effort for <unk>.
And while we've been more cautious about resourcing to separate relative to the later stage <unk> program. We're very excited about our progress we would anticipate accelerating these efforts were rats QQ opponent event that could further bolster our financial position, we will update investors on our progress with the <unk> program when appropriate.
With that I'd like to turn it over to our Chief Medical Officer, Dr. Richard Bryce. Thanks.
Do you have a niche and good afternoon everyone.
Following on from our last earnings call in March 2022.
We have successfully activated the multitude of sites around the world for our phase III <unk> study indeed difference they did like the sarcoma.
I will abbreviate later to <unk>, yes.
These include sites in the U S Europe and in Asia.
Our site plan builds in a degree of redundancy as it was difficult to predict how the pandemic was to evolve when we first started planning from the study in early 2021.
We also believe that our global site plan was able to mitigate the potential enrollments impacts that the Russia, Ukraine complex.
We're thrilled to announce that we are now over halfway enrolled in the 160 patient study.
And as <unk> pointed out we anticipate enrollment completion by the end of this year with top line data from the pivotal study in the first half of 2023, which is earlier than previously guided.
As a reminder, this pivotal trial compares <unk> monotherapy, that's our preferred dose of 260 milligrams dose daily for three consecutive days, followed by 11 days I'll refer to this as the three out of a 14 day schedule to the approved agent in Dallas <unk>.
Uh huh.
So in Dallas to the published median progression free survival and the DD Lps population of two two months.
In the prior 107 patient clinical trial with <unk> in which 53 patients with Didi Lps were enrolled Judy thing various doses and schedules.
The data previously presented demonstrated that those with the lowest median PFS rates were in the 30 patients receiving milligrams daily for either 21 or 28 days of 828 day cycle.
These dosing schedule as exhibit to the median PFS rate of six three months, which is almost triple out of Quebec to then from the <unk> population and the young Delek.
<unk> Registrational study.
In the 16 patients receiving the intermittent schedule of three out of 14 days at the 260 milligram dose.
The median PFS rate was seven four months.
And of note a phase III trial is powered to show a doubling of PFS benefit versus jump Dallas.
And as I mentioned earlier, we anticipate topline data readout from this study in the first half of 2023.
Our managed two basket trial in patients with P 53, wild type tumors with MDM two amplification that copy number 12 with greater is progressing as planned.
11 sites have been activated in the U S. At the end of April and additional just in time sites will be opened as necessary from referrals from the 10% tariffs genomic testing services.
We anticipate enrolling 65 patients across a range of solid tumors and using the same treatment protocol as in the Registrational mantle trial.
That is with Miller demonstrate dose of 260 milligram and the three out of 14 days scheduled.
We anticipate an early data readouts in the fourth quarter of this year and reporting patient responses duration of response and safety and approximately 10 evaluable patients.
Based on the progress made with our <unk> clinical program. Thus far we're looking forward to commencing two additional studies in the fourth quarter of this year.
As <unk> mentioned, we anticipate starting the mantra three study of <unk> in patients with Merkel cell carcinoma, who are resistant or refractory to checkpoint inhibitor therapy.
As a reminder, we believe the majority of patients with medical cell carcinoma up to 80% of them have a cancer induced by the polyamide buyers, which in juices MDM to over expression.
We are also encouraged by data from other MDM two inhibitor programs, revealing monotherapy activity in the tumor setting and.
Intense belief that there is an opportunity for an MDM two inhibits a program that may be better able to manage the on target Cytopenia toxicities.
And finally, we're excited anticipating the initiation of a full study before year end two evaluates our first combination regimen with Miller <unk>.
This study dementia false study.
We will evaluate the combination of <unk> and Roche has the centric oriented.
So that's your map.
In the phase <unk> study in approximately 30 patients with wild type P 53 advanced solid tumors, but also exhibit loss of the CDK and two AG.
As a reminder, we believe loss of the gene CDK NCAA and lots of its protein product <unk>.
It leads to increased <unk> levels.
<unk> is a natural regulator of MTM too.
There are a significant number of patients with wild type <unk> three solid tumors with advanced disease that exhibit lots of CDK in.
This is estimated at over 35000 patients per year in the U S.
As many at 6% to 7% so more of all solid tumors and.
And it's the second most common tumor pressure operation after P 53 mutations.
Demand for both studies will be primarily focused on confirming the safety of the combination regimen, but we will also evaluate efficacy.
With multiple clinical strategy at similar demonstrate underway, we're excited for all of potential new data.
So let me turn now over to our Chief Scientific Officer, Bob <unk>.
Uh huh.
Thanks, Richard and good afternoon, everyone first rain recently presented additional data relating to the mantra two patient population at the ACR annual meeting in New Orleans.
This work further detailed a variety of tumors that harbor high level MGMT gene amplification using <unk> copy number a threshold of 12 and showed a meaningful number of patients with lung breast bladder and gastro esophageal tumors amongst others.
Although CDK four is commonly co amplified with MDM two in Dedifferentiated Lipo circle and other sarcoma subtypes due to its proximity on chromosome 12. This presented work demonstrated a notable lack of CDK four co amplification in lung breast and bladder and gastroesophageal tumors amongst others, particularly at the cop.
Number 12 threshold.
Although the impact of oncogenic drivers remains unknown with respect to clinical benefit of <unk> two inhibition. This.
This analysis only found approximately 20% of patients with <unk> amplification.
Known oncogenic driver mutation.
Analysis of <unk> data demonstrated a worse overall survival for patients, whose tumors have MDM to copy number 12 or greater with wild type C. P 53, highlighting the unmet need in this patient population.
We presented a population analysis of over 50000 patients with solid tumors across the ACR Genie and TCA databases, which confirmed the presence of MDM to copy number 12 or greater with wild type <unk> 53, and one 2% of all cancer patients.
Second Dr. <unk> group at Dana Farber presented preclinical data last month at the second International Symposium of Merkel cell carcinoma, demonstrating robust activity of no downtown and in vivo Pdx models of Merkel cell.
This preclinical data supports our upcoming mantra three study.
Third <unk> will present, an abstract at the upcoming <unk> annual meeting in Chicago relating to the patient population eligible for the upcoming mantra for clinical study.
In addition to the tumor specific frequencies of CDK into a loss in the setting of wild type <unk> three range plans to present, new data supporting the rationale behind our first combination trial with no doubt a town and it has a loser.
Finally, we remain excited about <unk> 52 is a synthetic lethal target an internal research efforts at bringing our ongoing to advance this program.
And with that let me now turn it over to Nelson to review our financial results Alpha.
Thank you Bob and good afternoon, everyone I'm pleased to provide an update of our financial results for the first quarter ended March 31 2022.
I would also like to invite you to review our Form 10-Q filed today for more details.
For the first quarter of 2022, we reported a net loss of $17 4 million compared to a net loss of $6 8 million in the first quarter of 2021.
Research and development expenses were $13 6 million in the first quarter of 2022 as compared to $5 3 million in the first quarter of 2021.
The increase was primarily driven by R&D costs, mainly for our lead candidate Mila Demeton from the ongoing phase II mantra clinical study our ongoing phase II <unk> III study as well as personnel costs.
General and administrative expenses were $3 9 million for the first part of 2022 compared to $1 5 million for the first part of 2021.
Increase was primarily driven by higher third party G&A cost, including personnel insurance legal accounting audit and outside consulting fees.
As of March 31, 2020 to reign had $123 2 million in cash cash equivalents and short term investments and we anticipate that our 2022 year end cash position will provide runway into the first half of 2024.
We expect automotive demonstrate clinical programs to be well funded.
With that I'll now turn the call back to <unk>.
Thanks, Nelson again, our focus with the <unk> program has been on clinical execution, we're very happy with our rate of progress thus far with the anticipated start of the mantra three and mantra for studies by year end on top of the ongoing progress of both mantra and mantra to rein anticipates, a broad clinical effort promoted them at.
With a steady cadence of updates over the next two plus years in.
In particular for our phase III mantra study, we highlighted rapid enrollment of LIFO sarcoma and top line data anticipated in the first half of 2023 earlier than previously guided overall the rain team is poised to generate significant new data for <unk> that will potentially lead to a new targeted therapy for cancer patients.
I will turn it back to the operator to take your questions.
We will now begin the question and answer session.
To ask a question you May press Star then one on your telephone keypad.
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At this time, we will pause momentarily to assemble our roster.
Our first question will come from corn Jenkins with Goldman Sachs. You May now go ahead.
Hey, good afternoon everybody.
So I think you're expecting to have some patience from previous guidance.
Great and then about 30% and with ASC update later this year and so I'm curious what would you anticipate.
The first sedan or whatever else.
For the FDA to require.
Accelerated approval.
What kind of cohort five.
Thanks.
Thank you and thanks for the question let.
Let me turn that question over to Bob and just to reiterate the question I believe your question was.
What type of cohort size for mantra too.
The tumor agnostic baskets or do we think would be appropriate.
For our Registrational effort.
That correct.
Alright, so assuming you have 10 patients and that there are present or are there.
Yes.
Okay.
Yes.
Sorry, 10 patients.
And in the previous.
What was the second part of that.
I think previously you've said that 30% IRR is a reasonable expectation for that I'm assuming.
Assuming that's kind of in the range of where you are what should we expect for Cobra.
Hi.
Previously.
Well, let me first I guess, so in terms of cohort five needed for an accelerated approval. We can obviously look to prior example, so there are.
Private previous targeted therapies that have got accelerated approval in a diagnostic setting.
With approximately 50 to 60 page.
Patients.
Obviously that depends on the magnitude of the benefit.
Another thing.
Maybe if I just add.
That.
Yeah.
What is expected of an approvable agents.
Gnostic setting.
Currently the bar is set.
By our prior example, again with <unk> and MSI high with a response rate of 40%.
But we are following closely other targeted therapies that are seeking an agnostic approvals.
We will.
Follow that data closely in terms of clinical meaningful enough.
Typically patients with later line.
<unk> options, such as chemotherapy may experience response rates, and perhaps 8% to 12% range and so the bar for clinical meaningfulness, maybe quite a bit lower than 40%, which is the current lowest example of an agnostic.
Crude trucking.
Okay.
I guess is there a cohort side it sounds like it would be kind of a best case scenario, but is there a very competitive environment.
As you think about the future.
Okay.
Sure.
As we go forward.
Yes.
Sorry, we're getting a lot of back for noise from your Premier audio so we're trying to make out the entirety of the question, yes, but yes.
Alright, I'm at the airport do you mean therapy.
Okay.
So it's the size of the court if we have a 30% response rate duration of response in excess of five months, which is kind of.
What we think is clinically meaningful responses, we would expect the cord size expanded who may be in the 90 to 120 patient range.
Okay helpful. Thank you.
Our next question will come from Summit Roy Jones Research you May now go ahead.
Hi, Thank you for taking the question and.
And congratulations on progress on multiple fronts.
One quick question on months of trying to phase III trial are you looking into any.
Biomarkers to detect if there is any resistance mechanism going on I can't I can't to Cal binding that you appear to have a new debt.
That could cause a reduction lower.
Lower clinical benefit.
Hi, Simon Thanks for the question and that question with regard regarding clinical Biomarkers for the mantra to study correct.
For the month to month.
Trial in sarcoma.
Phase III just thinking ahead, if you see.
Listen.
Hum.
Predicted clinical benefit are you looking at Cal binding or this kind of biomarkers to see there.
Certain sub group is kind of pulling back.
The entirety of the quality doesn't.
Okay.
<unk> Hi, it's Richard Bryce here, so for the ongoing management study, we do have.
We're looking at make one which is a surrogate biomarker moving forward and.
The.
Bob is that we have will be going for.
Testing for MTM to.
Essentially downstream, but essentially that's what we're looking at in the context of mantra, which is a kind of a real web study moving forward.
Okay got it.
A quick question on the Merkel cell carcinoma, do we know the incidence of what percentage.
Patient express MDM to copying them, a greater than 12 akin to that bar graph presented called and indications.
Yes.
Merkel cell doesn't have India into gene amplification as far as we know there is protein over expression. So the volume of virus and Merkel cell leads to greater protein production, but not necessarily due to gene amplification.
And is that the same case with.
The CDN.
CDK into them.
Patients also more legal work production rather than gene amplification.
Thanks for that question, that's about double yes.
Slightly different mechanism there here the main mechanism of cm to.
Two dependence and CDK into a loss is that CD <unk> encodes a negative regulator of MDM too so loss of <unk> leads to increased activity of MDM too.
So all the same idea in terms of MDM to dependency.
Not through necessarily over expression of our genetic amplification of adventure.
Got it. Thank you again for taking the question.
Thank you.
Our next question will come from Yigal <unk> with Citi. You May now go ahead.
Hi, This is carly on for Yigal. Thank you for taking our questions. We have two questions first.
First can you talk about how patient identification and enrollment for mantra to our tracking relative to your initial expectations. I think you had laid out expectations for about a 1% positivity rate for the FDA to copy number greater than 12.
And then the second question is Michael Sarcoma, we saw that Boehringer Ingelheim had started a phase two three for their <unk>, two inhibitor, where theyre going straight into the frontline setting head to head versus chemo. So we wanted to get your thoughts on that strategy.
Mantra works, if you would consider a similar study can do.
Thank you.
Thanks, Charlie let me.
Start with the second question first I'll address the bringing on study. So I think one thing to point out with the <unk> program is.
The phase III strategy is meant to first pick a dose so theres a couple of arms to identify the appropriate dose before moving into the phase III component of.
Of their trial, so the phase two three.
Still going to be two aimed at determining the appropriate dose to carry forward.
But the second part of your question is if we see success mantra would we look at the first line setting I think it would be reasonable to assume that we would evaluate that opportunity.
And in terms of the first question.
That you asked about.
The months of two patient tracking.
So this is Bob <unk>. So in terms of mantra to we are definitely confirming that 1% actually closer to one 2% of all patients.
We are seeing these genetically identifiable patients.
And as we've said enrollment remains on track for mantra.
Okay, great. Thank you very much.
Okay and if your question. Please press Star then one.
Our next question will come from Michael Schmidt with Guggenheim Securities You May now go ahead.
Hi, guys. Good afternoon. This is <unk> on for Michael Thanks for taking our questions. We.
We have two questions. The first one on mantra congrats on the progress.
Just wondering is the earlier than expected top line, primarily driven by faster than expected enrollment in the U S or ex U S. And also could you confirm theres no changes on the assumption.
Question rates and.
And second question on <unk> two.
How should we think about the tumor reduction kinetics, I mean based on previous data with.
Unexpected response to happen earlier.
For example in the first two cycles, where this could be later.
Thank you.
Thanks again, let me, let me ask Richard to comment on the first question for the mantra enrollment and Bob on the second for mantra to Richard.
Sure. So I think your question was asking about.
Contribution to enrolment essentially for the mandatory U S. Ex U S. It's a global study and I think it's fair to say that contribution has been.
Across the board, so I wouldn't select one geography over another.
In terms of enrollment I think what it does do is.
Validate the unmet need out there in the.
The requirement for treatment for this particular indication.
I think the second part of your question related to <unk>.
Functions around the PFS rates have there been any changes to that and the answer is no.
Goal remains unchanged from the outset.
And regarding the second question.
The response kinetics and the mantra to study.
I'd say looking at the phase one data.
Which was.
Mostly either light bulbs are co locations, which don't have a high response rate in unselected non FIFO sarcoma patients. We just simply don't have enough data to make an estimate on response kinetics.
Can say that we have seen rapid responses in some cases.
Not enough.
To really determine what the expected or whether it will be similar to tyrosine kinase inhibitors typically show.
Bonds at the first scan so we just don't know yet.
Great. Thank you.
Thanks again.
This concludes our question and answer session I would now like to turn it back over to our niche of a lucky for any closing remarks.
Well, we want to thank everyone for joining us on today's update and we look forward to providing an update on the second quarter call. Thank you.
Yeah.
The conference has now concluded. Thank you for this presentation you may now disconnect.