Q4 2022 Rain Therapeutics Inc Earnings Call
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I would now like to hand, the conference over to your host today, Christy Corabelle ski please.
Please go ahead.
Thank you operator, and good afternoon, everyone with me today on the phone our Ava niche Milwaukee, Chief Executive Officer, Robert Doble, Chief Scientific Officer, Richard Bryce Chief Medical.
Officer, and Nelson cannot Chuan senior Vice President Finance.
During today's call avenues will provide an overall business update Richard will provide an update on <unk> clinical programs, Bob will provide an update on research efforts and Nelson will review the financials before we begin I'd like to remind you that statements made during this conference call that are not historical facts are forward looking state.
<unk> within the meaning of the private Securities Litigation Reform Act of 1995.
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 subsequent filings with the Securities and Exchange Commission all four.
Forward looking statements made during this conference call are based on management's assumptions and estimates as of today March 32020 to rein 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 for Lunky CEO of rain therapeutics of a niche.
Thank you Christie and thanks to everyone for joining us for our fourth quarter earnings call. In this most recent quarter and since the end of <unk> range continues to advance the mill of Dermatology program with two clinical trials currently active and enrolling and two additional clinical trials plan as.
As a reminder, we may refer to mill, Jimmy Tan as Miller on occasion.
First and foremost our 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 at the end of 2021, we exceeded the number of site Activations that we had articulated as a goal and continue to be on pace.
For all sites to be up and running by the end of the first quarter of this year.
The potential registration, enabling study there is no interim read with final data anticipated in 2023.
Richard will provide some more color here.
Second in November of 2021, we announced that the first patient had been dosed in the phase two tumor agnostic mantra to study. This trial will evaluate the signal finding basket trial across approximately 65 patients in the U S with solid tumors that exhibit strong <unk> gene amplification.
<unk>, we anticipate to reveal early data from this trial in the second half of this year.
Third we announced the mantra three study in the fourth quarter and articulated that it will be focused on patients with merkel cell carcinoma that test positive for the Merkel cell poly yoga virus.
Majority or up to 80% of Merkel cell carcinoma are induced by a virus. This virus induces MDM to protein over expression and as P 53 wild type.
Enroll second line patients relapsing your checkpoint inhibitors, where there is an immense unmet need.
We now anticipate this trial will start in the second half of this year, David upon progress of our first two trials. So that we made better control the timing of expenses as we strive to maintain our fiscal prudence.
Finally for our fourth trial for <unk>, which we are calling the mantra for study.
Where it intends to combine <unk> with Roche's PD L. One monoclonal antibody tens elysium bad in our first combination trial. This initial combination trial has a goal of confirming an appropriate combatant toiled dose for the two agents and evaluate the safety Tolerability and efficacy of this combination in a can.
Cancer population that could exceed 35000 patients per year in the U S. The mantra for study will represent another tumor agnostic basket trial. This time in patients with P 53 wall type cancers.
A large function of the gene CDK <unk>.
The mantra for study is anticipated to commence in the second half of this year.
We also held an R&D day in November of 2021, which featured several key opinion leaders in oncology along with members of <unk> management team will discuss the company's R&D program as well as select clinical and preclinical data. We encourage interested parties to review the materials on our website.
While we continue to focus on the most sensitive MGM two dependent cancers and have outlined four distinct strategies for melanoma Chan, it's perhaps kita emphasized that our cash balance is sufficient to complete all of these trials and should help inform the best manner to deploy future investment into the mellow Demeton franchise, we're very.
Excited about the potential for a range of opportunities for Miller, having a meaningful impact on patient care.
Guarding our research program for inhibitors, a Rad 52, the preclinical work continues to move forward and we're very excited to note substantial improvements in both potency and selectivity of rain generated compounds versus the initial set of compounds. We acquired from our licensing efforts. However in order to prioritize our resources.
On the mill of Derma 10, clinical trials to ensure ample cash cushion for the key data inflection points and in light of what the bunch of capital markets have been doing we will moderate the pace of expansion for the Rad 52 effort, we plan to update investors on next steps for this program as details become available.
With that I'd like to turn it over to our Chief Medical Officer, Dr. Richard Bryce. Thank.
Thank you <unk> and good afternoon, everyone.
Although we know from our last earnings call in November 2021, where we announced we are progressing that site activations dropped the U S and rest of the world for our pivotal phase III <unk> study Mila demeton compared to <unk> in Dedifferentiated Lipo Cocomat I can report that we were ahead of expectations the site Activations.
At the end of the year of 2021, and we anticipate having all sites activated before the end of this month.
Patient enrollment continues as expected.
As a reminder, this pivotal trial will compare military time monotherapy, that's our preferred dose of 260 milligrams and three out of a 14 day schedule to the approved agent in Dallas or Trabecular, <unk>, which is a published median progression free survival and the Dedifferentiated lipo sarcoma patient.
<unk> of two two months.
In the private 107 patient clinical trial of <unk> in which 53 patients with Dedifferentiated Lipo <unk> enrolled the lowest median PFS observed with $6 three months.
And our preferred dosing schedule, a median PFS of seven four months as observed representing a greater than threefold improvement, but as trabecular them.
Our phase III trial is powered to show a doubling of benefit.
We anticipate final data in 2023, but we will refine that guidance as we move through enrollment.
I am pleased to announce that the first patient was dosed in a second trial the mantra two basket trial in November .
The mantra to study is currently planned to run only in the United States and all primary sites are expected to be activated by the end of this month with additional just in time sites being opened as necessary from referrals from the 10% tariffs genomic testing services.
This trial is open to patients with tumors that are P 53, wild type and have a specific threshold of MDM two amplification.
As previously reported we have defined the MTM two amplification for the purposes of the clinical trial as a minimum gene copy number of 12.
And as discussed in the third quarter call. This threshold is chosen because the hygiene amplification that these levels has been shown to essentially exclude concomitant P 53 mutations, thereby ensuring M. D M too as the oncogenic driver in these tumors.
We anticipate enrolling 65 patients across a range of solid tumors and the treatment protocol is the same as in the Registrational Manta trial.
That is with Miller Demeton does the 260 milligrams orally once daily for three consecutive days out with 2014.
We anticipate an interim analysis and the early data readout in the second half of this year.
Also as announced in November we plan to evaluate the efficacy of Mila Demeton as a monotherapy for the treatment of patients with medical cell carcinoma in the second line setting.
He said patients who are refractory or resistant to immune checkpoints inhibitor, which we call the mantra three trial.
We note MDM to inhibition appears to have gained validation in the medical cell carcinoma.
Based on all the programs.
Whereas we believe the improved Tolerability of Miller <unk> may offer improved responses and durability.
In the second line setting post checkpoint inhibitors, the commonly used chemo doublet Cabo.
Carboplatin and Etoposide exhibit very short durability of response and noticed survival benefits has been published for treatments in this setting.
We anticipate commencing the mantra three trial in the second half of this year.
And we believe this indication is a high probability of a favorable outcome.
At the beginning of January .
We announced plans to conduct a phase one clinical trial manager for to evaluate the safety Tolerability and efficacy of <unk> in combination with roche's <unk> in patients with advanced solid tumors with loss of CDK into a gene function and.
Wild type P 53.
We'll talk more about the mechanism shortly.
This will be a dose escalation study design, where we will start at the full doses of both Miller Demeton.
Again, the $2 60 milligrams and three out of 14 days schedule.
And the approved dose of the lithium app centric on the Q4 week schedule.
We will reduce the dose of mill downtime that we observe a dose limiting toxicity.
However, as we would not anticipate any overlapping toxicity between millet demeton lithium at this trial could effectively become a 30 patient efficacy signal finding basket trial across a range of solid tumor types.
We anticipating starting manager for in the second half of this year.
Upon a favorable safety. They don't subsequent phase II clinical trials may evaluate combination of Miller, demeton and the Tesla <unk> and various additional tumor types.
To conclude we have outlined for clinical trials familiar demeton led by the flagship mantra pivotal phase III trial in life is to come out.
The manager too and manager for trials reflect unique basket study approaches.
With mantra three in Merkel cell carcinoma, representing an important unmet medical need.
We look forward to presenting some data later this year from the managed two basket study.
And the mantra three and <unk> four trials will start in the second half of this year.
Let me now turn it over to our Chief Scientific Officer talked about Devil Paul.
Thanks, Richard and good afternoon, everyone since acquiring <unk> in September 2020 range team has been working diligently to identify and validate the most relevant cancer populations for this MDM two inhibitor or.
Our work has recently culminated in the presentation of multiple abstracts at conferences in October 2021, including the ACR NCI EUR TCE virtual International conference on molecular targets and cancer Therapeutics highly.
An important preclinical collaborations with researchers around the world.
We also hosted our first rain research and development day in November 2021.
This event featured both clinical and research experts, who highlighted multiple opportunities for the use of mila damage in different tumor settings, where <unk> plays a critical role.
These presentations provide support for <unk> clinical strategy and prioritization of Dedifferentiated Lipo sarcoma, an M. D M. Two amplified agnostic tumor strategy and Merkel cell carcinoma.
These presentations also helped to provide the basis for exploration of clinical trials and other indications.
As breast cancer and other larger cancer population.
More recently, we were excited to announce an initial phase one clinical trial mantra for as part of a new collaboration with Roche for the supply of the Tesla lose about where to centric.
As <unk> stated the mantra for trials anticipated to enroll patients with any solid tumors harboring CDK into a loss and wild type <unk> 53.
Did he can do a encodes for the tumor suppressor <unk> 14, arf and inhibitor of MDM.
And the loss of <unk> 10 to a may lead to M. D M two dependent cancers.
Did he can do a alterations are very frequent enhance <unk>.
Loss of CDK into a occurs in the context of wild type <unk>, three and more than 35000 patients per year in the United States.
Preclinical data in a large array of cell lines demonstrates that the debt using only the genetic selection criteria of CDK into a loss and wild type <unk> three predicts for millet Amazon sensitivity.
In vivo data demonstrate millet, Amazon induce tumor growth inhibition in several tumor xenograft models with CDK into a wall.
Notably our Syngenta a tumor model with Citi can do a loss shows the exciting potential north Amazon combination therapy, the combination of knowing Amazon with a checkpoint inhibitor demonstrated significantly improved activity versus either agent alone.
We also know clinical reports showing checkpoint inhibitor resistance in tumors with CDK into a wall.
We believe reactivation of P 53 by M <unk> inhibition will enhance immune surveillance.
A mantra for trial is anticipated to commence in the second half of this year subsequent phase III clinical trials evaluating the combination of melanoma town and it has a loser mab may span various additional tumor types.
And with that let.
Let me now turn it over to Nelson to review our financial results Alison.
Thank you Bob and good afternoon, everyone I'm pleased to provide an update our financial results for the fourth quarter and full year 2021.
I would also like to invite you to review our Form 10-K filed today for more details for the fourth quarter of 2021, we reported a net loss of $18 million compared to a net loss of $5 4 million in the fourth quarter of 2020.
Research and development expenses were $14 7 million in the fourth quarter of 2021 as compared to $4 2 million in the fourth quarter of 2020.
The increase was primarily driven by R&D costs, mainly for our lead candidate from the ongoing phase it without mantra clinical trial, our ongoing phase II tumor agnostic basket trial, or a month or two as far as personnel costs.
General and administrative expenses were $3 4 million for the fourth quarter of 2021 compared to $1 3 million for the fourth quarter of 2020.
The increase was primarily due to higher third party G&A costs, including personnel insurance legal accounting and audit and outside consulting fees.
For the full year 2021, we reported a net loss of $51 4 million compared to a net loss of $21 1 million in 2020.
R&D expense as the main driver of our overall spending R&D expenses were $4 8 million in 2021 as compared to $15 4 million in 2020.
The increase was primarily driven by cost mainly formula demonstrated from the ongoing mantra and mantra to clinical trials as well as personal costs. We completed an IPO in late April 2021, which generated net proceeds of $121 5 million.
As of December 31, 2021 reign had $142 million in cash cash equivalents and short term investments and we anticipate that our 2021 year end cash position will provide runway into the first half of 2024, including completion of all our ongoing.
And planned clinical trials with an ample cash cushion for the phase III data timeline LIFO sarcoma.
With the current capital market condition in the biotech industry, we will continue to be more prudent with Cabot bulbs for you where they just did a generation formula demeton across a diverse set of <unk>.
With that I'll now turn the call over back to <unk>.
Thanks, Nelson without a doubt the current capital markets environment for biotech signals for many companies that further financing may be challenging and it rain, we were comfortable with that based upon the strength of our balance sheet.
Brain has been built around efficient trial designs and lean operations, we will continue to make efficient use of our capital resources in order to achieve key value inflection points for our company and our shareholders with that we will turn it back to the operator to take your questions.
Okay.
And thank you as a reminder, or ask a question you will need to press star one on your telephone to withdraw your question press the pound key please standby we compile the Q&A roster.
And our first question comes from Yigal <unk> from Citigroup. Your line is now open.
Hi, guys. Thanks for taking my question.
Just a question on the <unk>.
Umbrella just wondering was there any scientific reasoning behind picking a PDL one as opposed to a PD one doesn't matter, which way you do that when you combine the milligan.
Are you all thanks for the question I'll hand, it over to Bob. Thanks for the question at this time no. We see no significant scientific differentiation between PD L. One PD, one or significant differences in clinical activity. So at this time, we don't.
We have reason to distinguish between the two for the purposes of the combination trial.
Trial.
For mantra for.
Okay Gotcha.
Then since you are beating targets on site activation for mantra, just curious if youre able to narrow down at all whether we're going to get the top line in the first or second half of next year.
Yes, it's a great question, we're not going to refine that guidance just yet.
We will do that we will do that.
You know when we can and we're not just not doing that just yet.
Okay.
And then one other question just.
I want to get your thoughts on the competitive data from mirror CD Greater K T.
Q3.
So when you saw the latest slides, where they're showing some data in comparison to the 50.
Three small molecule inhibitors.
They're they're arguing that MTN dew degradation as a better approach than ambition.
I'm just curious if I could get your thoughts on.
Thanks.
Yeah happy happy to address that and I think first of all.
It certainly does further validate that <unk> is a target of interest and certainly has broad utility. So so we're not surprised that we're seeing other competitors enter the space and we certainly weren't surprised to see them benchmark their early data against against.
No Demeton program.
So let me hand, it over to Bob to talk through Mechanistically in terms of the greater approach versus versus our approach.
Yeah. Thanks for the question I think all in terms of the two.
Greater approach.
Obviously this is a.
<unk> way to inhibit MDM too.
At rain, we still feel that one of the central problems and MDM to inhibition, which we believe that we have solved our dosing strategy is the on target toxicity.
That comes with M. D M. Two inhibition in normal cells, such as hematopoietic precursor cells and.
And it's not clear that are do greater strategy addresses that on target toxicity.
I think as you know the molecule.
The we're working with <unk> 32, a mill with Amazon is actually quite potent at inhibiting <unk>.
Okay.
Okay.
And then regarding the cash preservation.
Any more detail on the steps you're taking there too.
Reserve cash.
Yeah.
We can provide as we've of course always maintain a pretty close eye on their cash burn.
One of the comments that we did make was.
That we minimized the expansion of the head count of the company and its one of the ways that we're moderating expense, where we're still a modestly sized company has a phase III entity.
We're still very small physical footprint in terms of real estate relative to comparable companies.
And all of our studies right all of our studies are rather modest in size. So they don't require a level of cash burn that.
We see typical in the biotech space and the gating mechanism right. So we have we've announced the subsequent two studies mantra three and four we have a tremendous amount of control in terms of when we when we flip the switch and we want to flip the switch and turn those on at a time when we know that we have a clear line of sight towards.
Final data from mantra.
We preserve.
The integrity of completing.
Completing that study with an ample amount of cash cushion. So the amount of control we havent turning on various expenses is essential.
Got it thank you very much.
Thank you and our next question comes from Michael Schmidt.
Guggenheim Securities. Your line is now open.
Hey, good afternoon. This is ebay on for Michael Congrats on the progress and thanks.
We're taking our questions.
I guess a quick one from us.
To some recent literature siddiqi into a sometimes co deleted.
<unk>.
So first of all do we know how frequent is the code deletion and.
And dad keys, how would targeting CDK and two way through M D and <unk> inhibition.
Positioned relatively to you know some of the other strategies to targeted tap.
Thank you.
Thanks for the question you gave let me turn that over to Bob.
Yes, thanks for the question.
The code deletion of M tap with CDK <unk> is thought to be incredibly frequent impact probably approaching 100%. It's actually the next adjacent Jean <unk>. So it is probably code deleted.
And the vast majority if not all city can do a loss tumors I think the relative contribution of the two genes.
Being worked out and weather.
Matt <unk> five inhibitors may have potential.
Potential effect in CDK into a loft tumors or if there are other criteria that need to be a factor.
Factored in.
Still remains to be known but we have been.
Thinking about this question with regard to city Canterbury law, often they use of our Mila Dallas.
Our preclinical research program.
Got it that's helpful. Thank you.
Thank you.
And our next question comes from Joe Ken Zaslow from Piper Sandler.
Line is now open.
Perfect. Thanks, guys for taking my questions here, maybe the first one on mantra to I'm wondering if you could speak to the early experience around screening and identifying patients with MDM, two amplification and where expectations are currently for the interim readout expected later this year in terms of number of patients to an extent a follow up.
Thanks, and I have a follow up.
Thanks, Joe Let me turn that one over to Richard.
Hi, Joe Thanks for the question so mantra to as you recall, we kicked off in November of last year, but that site activated first patient and we are still in the process of activating sites. So it's still very early in the game here.
Most of the sites.
Really won't be open until the end of this month. So it's still it's still a little bit.
Early to comment on that in the distribution tumors and other things that are sort of implicit in the question that you asked I think generally in terms of what data, we're going to be able to share towards the end of the year.
<unk> expressed opinion is that we hope to come up with a data set of somewhere around 10 to 12 patients with a meaningful duration of follow up in other words.
Four or five months something of that order. So that's what we're aiming to do and we're tracking towards that at the moment, that's as best as I can answer at this time.
Okay. Thanks, that's helpful and then a follow up on mantra for so so Richard you mentioned the dose escalation.
Sort of built in design there I'm wondering if you could speak to maybe what gives you confidence that you could achieve.
<unk>, the full monotherapy doses for each and whether the FDA needs to sign off on this design given.
Maybe they are recently pushed around identifying the minimally effective dose so I'm not sure if that applies to combination strategies as well. Thanks.
Sure. That's fair question. So I'll answer the second part first which is that.
We will obviously submit the protocol to the IND and the FDA will have the opportunity to comment, but we don't explicitly need.
By into the design that that's something that.
We do at risk the precedent has already been said I'm sure you're well aware the.
Our previous study with an Indian two inhibitor has been run with a checkpoint inhibitor following a very similar.
Process. They they had a dose escalation, but actually ended up with the full dose of both the checkpoint inhibitor and the <unk> inhibitor and I think given what I said before in the in the introduction here. There are no overlapping toxicities, we wouldn't expect any reason to deescalate with.
Compromising the Tolerability, if you like of milligram or vice versa. So we're we're very confident that we.
We can save time effort money in patients by going into the top dose that the standard monotherapy doses and see what happens take it from there.
Okay got it thanks for taking my question.
Thank you. Thank you.
And our next question comes from Corinne Jenkins from Goldman Sachs. Your line is now open.
Hi.
Thank you for taking my question I'm on chart, two I wanted to ask about it.
B J E T y.
Did he die.
C C.
Brian .
Who are you thinking about expanding into specific cohorts.
I don't think we got the first part of the question I think we can address the second part.
The second part I heard is how we're thinking about expanding to additional.
Tumor types or cohorts there.
Let me turn it over to Richard to talk about the second part and then maybe well have you repeat the first part of your question Richard sure. So thanks cream for the question and forgotten the second part so.
The study is currently designed I think we are well aware.
We've announced before is 65 patients we have a cap on the number in any particular tumor type that comes in and that's around 12 or so.
And so really what we'll be looking at festival, we setting off on a on a tumor agnostic approach, we would expect and hope to see similar responses across all tumor types given the mechanism of action there shouldn't really be any differentiation between them but.
It will give us an opportunity as the data accumulates to see whether there is.
<unk> success is greater responses greater durability of responses and some types and others that may given the indications of sort of move forward.
One particular strategy or one particular tumor type or basket.
Types within that but I think the.
The beauty of this particular trial design is that.
It gets the opportunity to look at if you get suboptimal responses you can look at combination strategies you can look at building and other things for example.
C D can enter a deletions on top of that as a separate cohort. There's all sorts of ways. You can play this game within the silicon starts at the basket study as it stands so there's many many opportunities and I think it's just a question of waiting to see where we are towards the end of the year and into 2023 is based on mature it and see what see what we're actually seeing.
Can you repeat the first part of the question.
Wow.
Do you think you need cheap.
We're trying.
To do that.
Okay.
I'll go back to electrification.
I think I heard what what quality of data would we look from the mantra to study to go to the FDA.
Compelling Bob would you like to talk to that.
Yeah. So we've thought a lot about what would be compelling.
Efficacy data in the context of a an agnostic or basket study.
When we initially designed.
Mantra too.
We thought that the benchmark.
For success based on the limited data diagnostic approved drugs, which include.
<unk>.
Checkpoint inhibitor or the checkpoint inhibitor demonstrated a response rate in the range of about 40% in the basket study.
So our study was designed.
To achieve a 40% response rate with a lower.
Lower boundary.
Comprehensible.
25%.
Since that time I think there are programs that are developing that we believe may have lower response rates and maybe meaningful and in fact, when we think about therapies for late line cancer patients were.
Single agent Chemotherapies or are typical of a standard of care and response rates, maybe as low as you know single digit percentages or.
Perhaps low teens with.
So that bar could be substantially lower than 40%, but that's how we've been thinking about.
Trial.
The clinical efficacy that we'd need to see and that of course that would need to be coupled with reasonable durability as well probably in the range of five to six months.
Does that answer your question.
Okay.
And thank you.
I am showing no further questions I would now like to turn the call back over to <unk>.
Belonging for closing remarks.
Well. Thank you everyone for dialing in for the fourth quarter earnings results, we look forward to providing an update shortly at the end of the first quarter of 'twenty two thank you.
As a reminder to ask that.
This concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
Yes.
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Yes.
Thank you.
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Perfect.
Okay.