Q4 2021 Oncternal Therapeutics Inc Earnings Call
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Greetings and welcome to <unk>.
<unk>, Inc, Q4, 2021 financial results conference call.
At this time all.
All participants are in a listen only mode.
A question and answer session will follow the formal presentation.
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These stars Ito on your telephone keypad.
As a reminder, this conference is being recorded.
I would now like turn the conference over to your host.
Richard Vincent CFO .
All internal therapeutic.
<unk> Inc. Please go ahead Sir.
Thank you Peter.
Good afternoon, everyone and thank you for joining us today.
Joining me on the call. This afternoon are our president and CEO , Dr. Jane Reitmeier, and our CMO, Dr. Elaine Y'all Street.
Today's call includes a business update and discussion of our 2021 fourth quarter and full year financial results, which will be followed by Q&A.
Today's press release and a replay of today's call will be available on the Investor Relations section of our internal website for at least the next 30 days.
We filed our 10-K for the full year of 2021 earlier today.
Please note that certain information discussed on today's call is covered under the safe Harbor provision of the private Securities Litigation Reform Act.
We will be making forward looking statements during this call about future events such as.
Our business and product development strategies, the timing of initiation of our preclinical and clinical studies.
The potential for our Zillow 301 study to support a BLA submission.
<unk>, a planned interim data updates and the timing of our regulatory filings and submissions.
Our actual results could differ materially from those stated or implied by these forward looking statements.
Risks and uncertainties associated with our business.
These forward looking statements should be considered in conjunction with and are qualified by the cautionary statements contained in today's press release, and our SEC filings, including our Form 10-K for the full year ended December 31 2021.
This call contains time sensitive information that is accurate only as of the date of this live broadcast March 10 2022.
We undertake no obligation to revise or update any forward looking statements.
Like the events or circumstances occurring after the date of this call.
With that it's my pleasure to hand, the call over to our CEO Dr. Jim Reitmeier.
Thank you rich and good afternoon, everyone.
And I'm turn on we are advancing a diversified and robust product pipeline with clinical and preclinical product candidates that target cancers with unmet medical need.
During the fourth quarter of 2021, we made significant progress in the development of our entire pipeline, including.
Including the seal, Alberta, Mab or investigational potentially first in class humanized monoclonal antibody that binds with high affinity to a biologically important epitope on RAR, one otherwise known as <unk> receptor tyrosine kinase like orphan receptor one.
We reached consensus with the FDA on the design and key elements of our planned global Phase III study Zillow 301, designed to treat patients with relapsed or refractory mantle cell lymphoma with zillow burden that in combination with Ibrutinib and.
And we also received positive feedback from the agency on the key elements of our <unk> development program, we expect to initiate the phase III study in the second quarter of 2022.
Okay.
Our commitment to this study and the positive developments on the regulatory front. We're all supported by clinical data from our ongoing phase one two clinical trial.
<unk> plus ibrutinib for patients with mcl or CLO.
With efficacy and safety data that are encouraging compared to historical results with Ibrutinib alone.
Our CMO Salim Yancey will summarize these exciting clinical results in a moment.
We also made progress in our cell therapy program, we select we selected eight O eight and autologous car T targeting <unk> one is our lead candidate <unk>.
The lengthy virus manufacturing campaign is progressing to plan Atlantic.
And we have very encouraging results for the number of expanded T cells. The.
The car expression and the T cell phenotypes for the potential GMP car T cell generation process development program.
We had a very productive pre IND meeting with the FDA.
And IND, enabling preclinical work is on track for a mid 2022 IND submission.
<unk> will also discuss the planned clinical development plan for our lead candidate.
Research collaborations with cellular already and with the Karolinska Institute continued to generate supportive data for our next generation off the shelf <unk> based cell therapies.
We are also very excited about five three for our lead candidate androgen receptor or <unk>.
Inhibitor.
At our R&D day in January we presented detail about at five three fours novel mechanism of action as a dual action androgen receptor inhibitor or Dara D. AHRI, which also induces degradation of the androgen receptor.
Our diaries appear to be highly differentiated as we believe they interact with both the end terminal domain or N T D and the ligand binding domain R. L. BD.
Our inducing Ah <unk>.
Inhibition and degradation.
Preclinical data presented at the ACR NCI RTC virtual International conference on molecular targets showed that 534 exert anti tumor activity in clinically relevant prostate cancer models, including those with <unk>.
<unk> vacation and dilutive mind resistant.
Or that express androgen receptor splice variants, such as <unk> seven.
These data suggest that arc 534 could play an important role in addressing unmet needs for prostate cancer patients with advanced treatment resistant disease.
And finally, we presented interim clinical data from the ongoing phase one two study of 2016, our investigation on targeted small molecule inhibitor of the <unk> 26 transformation specific or ETS family of uncle proteins at the <unk>.
2021, virtual annual meeting too.
Two patients with relapsed refractory Ewing sarcoma continue to enjoy durable complete responses.
<unk>, including one patient who had a CR for 24 months on treatment and continues to have no evidence of disease off treatment after several months.
We continue to explore optimizing the $2 16 treatment regimen for patients with Ewing sarcoma and are currently enrolling a new cohort of patients being treated with single agent <unk> 216, using an intensified dosing schedule.
Let me now turn it over time Colonel CMO, Dr Helene sheet.
Thank you Jim good afternoon, everyone.
As a reminder, our recently announced phase III study zealously, all one will randomize patients with relapsed or refractory mcl, who have only had stable disease or reach a partial response after receiving corps months at Aqua <unk> monotherapy.
And we randomize them to receive either blinded me longer to map or placebo plus ibrutinib.
This study may provide to potential approval.
And that's the reason the approval based on overall response rate or overall plus.
Duration of response or New York.
And second FDA approval based on progression free survival or PFS as a primary endpoint.
Additionally, we are planning to conduct Zillow three O. Two an open label companion study of Zillow hooked them up lots of Britain or patients who have progressed quite aggressive disease. During the gwich'in if monotherapy run in all studies Zillow two <unk>.
And the results of this study could support a third label indication.
This innovative study.
May support both I'm escalators approval and final approval and single study.
We plan to randomize roughly 250 patients.
And we currently expect to reach the accelerated approval all of our endpoints and as early as two years.
After the initial patient is enrolled.
The final approval PFS endpoint and as early as three year after enrolling the first patient.
We are now in the final study ramp up phase.
We have selected a global Seattle to support operational execution execution, and we expect to initiate the study.
Quarter of this year.
As Jim mentioned, we are.
Entering this late clinical stage.
<unk> supported by very encouraging data from our ongoing phase one two clinical trial of <unk>.
Alberta mob in combination with Ibrutinib.
The total study.
Presented at the Ash meeting in December 2021.
The overall response rate of 81% and the CR rate of 35% for patients with Mcl.
<unk> was the low watermark closer but isn't it.
This compares favorably to the historical of 66% and 20% for Ibrutinib monotherapy, respectively.
Median PFS.
$35 nine months.
All patients with a median follow up of 14 four months.
Which also compares favorably to the historical PFS of 12 eight months.
Mono therapy.
The CLO data were also very encouraging was the landmark PFS of 100% at 36 months of where.
CLI patients who have previously received one or two prior lines of therapy.
Which compares favorably to historical Ibrutinib monotherapy.
Football around 75% or 36 months.
The combination of the over to Matt and Bruce and it continues to be well tolerated.
A safety profile consistent with or improved compared with historical data for Britain monotherapy.
For example in patients with Mcl grade three and four neutral field decreased well documented and only nine 7% of the patients with zillow hooked them up closer Blitz in it.
229% of Ibrutinib alone.
Additional study.
Regarding.
The lead candidates of our autologous <unk> targeting car T program.
We had productive pre IMD meeting with the FDA.
And we are on track to submit our IND in the mid in the middle of this year.
We also recently established a very experienced cell therapy scientific advisory board and are close to selecting major academic centers and the clinical sites.
Our proposed first in human study will enroll patients with relapsed or refractory hematologic malignancies, including those who have failed CD 19 car T cell therapy.
I will now turn the call over to our CFO Rich Vincent to review, our financial results and upcoming milestones.
Thank you Celine.
Our grant revenue is derived from a California Institute for regenerative medicine, or CERN Grant to the board and to research and development grants from the National Institutes of health or NIH and.
In October 2017, sovereign awarded an $18 3 million grant to researchers at the UC, San Diego School of Medicine to advance our sole study.
We are conducting this study in collaboration with UC, San Diego and expect to receive approximately $14 $4 million in development milestones under our research supports throughout the award period that expires in the first quarter of 2022.
In the third quarter of 2021, the NIH awarded the company to research and development grants for up to $2 million.
Support preclinical activities for the companies aren't $5 34, and Oct $2 16 programs, including <unk> 7 million payable to sub awardee.
Our grant revenue was <unk> 6 million for the fourth quarter ended December 31, 2021, and $4 3 million for the full year 2021.
Our total operating expenses for the fourth quarter ending December 31, 2021 were $8 6 million with $1 7 million in noncash stock based compensation expense.
And were $35 7 million for the full year 2021.
With $5 9 million in noncash stock based compensation expense.
In the fourth quarter research and development expenses totaled $6 million and general and administrative expenses totaled $2 6 million for.
For the full year 2021 research and development expenses totaled $24 1 million and general and administrative expenses totaled $11 6 million.
Asked for the fourth quarter was $8 1 million for a loss of $1 six or <unk> 16 per share basic and diluted for.
For the full year ended December 31, 2021, our net loss was $31 3 billion for a loss of <unk> 64, 64 per share basic and diluted.
As of December 31, 2021, we had $98 million in cash and cash equivalents and no debt.
We believe these funds will be sufficient to support our operations into mid 2023.
We have and will continue to manage expenses carefully and we'll explore all potential sources of capital to enable us to reach our milestone.
As of December 31, 2021, we had $49 4 million shares of common stock outstanding.
With respect to upcoming milestones for our <unk> program, we expect to initiate the global Registrational Phase III study Halo 301 in the second quarter of 2022.
We expect to report an interim clinical data update for patients with Mcl and CLO treated with Zillow Berta math plus ibrutinib from our ongoing study in the second quarter of 2022.
We also expect to have a phase <unk> investigator sponsored trial of <unk>, plus docetaxel initiated for patients with metastatic castration resistant prostate cancer in mid 2022.
On the cell therapy front, we plan to submit our first IMD pronged eight O eight our autologous <unk> car T cell therapy candidate in mid 2022.
<unk> 534, our lead product candidate, we expect to initiate IND, enabling <unk> toxicology studies and GMP manufacturing in the second quarter of 2022.
For 2016, we expect to report updated interim clinical data for patients with young sarcoma treated in the dose intensify the expansion cohort in the fourth quarter of 2022.
Now I will turn the call back over to Jim.
Thank you rich.
We are pleased with the progress in 2021 and look forward to multiple catalysts in 2022, especially the initiation of our global Phase III <unk> study.
And also submitting our <unk> car T IND application as well as advancing our direct program towards the clinic.
Our strong balance sheet will help us navigate this historically challenging macro environment.
We plan to focus our resources on areas of high unmet patient need where we believe our product candidates can make the greatest difference for patients.
Thank you for joining us today, and we look forward to updating you appear to be the remainder.
<unk> 2022.
That I will turn things back to Peter for the Q&A portion of this afternoon's call.
Thank you.
At this time, we will be conducting a question and answer session.
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One moment please.
Four questions.
Our first question is from.
I was just saying with Oppenheimer.
Please go ahead.
Great. Thank you Peter.
Just a couple of questions Jimmy.
Jim and team and thanks for the updates.
One is just for onto easily.
One car T.
What could a clinical trial look like.
Would be sort of the basket trials monotherapy combo with Ibrutinib.
And then what specifically are the learnings from the word of mouth.
NPL in CLO study that kind of help you.
Designing those those car T trials.
I just got a couple of quick follow ups.
Thank you <unk> I'll start with the second question and so.
We're moving into the car T clinical trials.
With an increased sense of confidence that we are capable of targeting ROI one specifically.
And as such that the.
The car Ts are expected to primarily interact with tumor cells and we're hoping to see a minimal cross reactivity with normal adult tissues, which may.
Offer.
Mainly to an acceptable safety program.
We are.
We are.
Also.
<unk> to learn.
Roger one as is important in large numbers of hematologic malignancies, which is where we will do that first clinical trial.
I will turn it over to Selene to ask to answer your question about the general shape.
The phase one study for the eight O eight <unk> car T.
Yes, Thanks, Jim.
So we're planning actually to do our first in human.
Got you.
No.
I think in the dose escalation phase we try to not mixed patient population was specifically probably can it be in lymphoma, but once we reach C.
Therapeutic dose.
And recommended phase II dose this is where we would start to some expansion in different.
Indications.
Does that answer your question I would touch yep.
Okay.
Helpful, but is it I assume.
To be clear.
And I might've missed that.
You will include a broad range of patients.
The initial.
So when that happens when you get into the expansion part of the car T trial.
The plan is when we get to the expansion because I think it.
Usually car T. A FDA wants you to have a very specific safety population in the dose escalation not to have it.
Like a mixed group.
Yes, yes.
Let me let me, let me add that we do think that.
We do think that lymphoma is a.
As an acceptable.
Small basket I guess for the for the initial clinical trial population.
Great.
And then just would you be using any kind of.
<unk> or any other.
One of the small molecules and combining all that also will you wait to do that if you're going to do that and when you get to the expansion expansion part of the trial.
We will study the car T alone initially so that we're sure we have a clear picture of its safety profile by itself and then we will consider augmenting and with additional factors later.
Great. Thank you Jim and then last question is.
Just on.
Ewing sarcoma.
Project.
Yeah.
There are 216, you've got the two.
Really nice complete responses one for more than 24 months.
When we get to the latter part of this year and you are looking for that high dose.
Data what is the hurdle you're looking for in order to continue on with the project I mean, what would you like to see.
In order to go to the next steps and thank you for all the questions.
Sure hard charging I'll take I'll take your last question as well so so so.
We're looking for an indication that the true response rate to Teekay to 16 is around.
At least 20% and that would be.
Partial response.
Incomplete responders.
Yeah.
Great. Thank you Tim.
Mhm.
Thank you. Our next question is from Colin violence with Northland Capital markets. Please go ahead.
Great. Thanks for the question and congratulations on progress.
How do you see R&D spending ramping up throughout 2022, considering the initiation of the xylem trials and also obviously the other R&D programs that are ongoing thanks.
Rich.
Sure. So as we mentioned we ended 2021 with about $91 million in cash and cash equivalents with no debt on the books a decrease of.
Just under $7 billion for the fourth quarter.
We do not provide guidance on a quarterly or annual cash burn we do anticipate that our current cash resources are sufficient to fund our planned operations into mid 2023.
Yeah.
Yeah.
Got it thanks.
Thank you. Our next question is from call it <unk> for them.
<unk>. Please go ahead.
Yeah. Good afternoon, thanks for the update.
My first question is four five to four.
Well for them and all of them.
Ligand binding domain, but how stable is the binding.
In the absence of the ligand binding domain because a lot of.
The L D D.
But I think we're buying at the same ligand binding domains like mine.
Fine.
Yes.
Barry This is Jim those are those are both good questions. So.
We are seeing very satisfying.
Activity, both in vitro and in vivo models.
Models of prostate cancer that have lost the binding the ligand binding domain. So we do believe that the N terminal binding is sufficient to inhibit prostate cancer.
On the ligand binding domain side, it does appear to bind differently than <unk>, because we are seeing activity.
In Angelina mine resistant strains.
Strange or lines of prostate cancer.
Yes.
Got it and Oh, the Laguardia mob.
Do you see an opportunity.
Pardon me.
Non small cell lung cancer patients I believe there have been some studies that have shown saga survival benefit with GPI, one question or Xbox one.
Yes.
We've noticed those those data as well.
We are we're doing some preclinical work.
In lung cancer, right now, particularly intriguing.
The result that we are pursuing.
As a publication, suggesting that.
<unk> cancer cells that have become resistant OCD Merton Ned might be re sensitized to Oc Merton and treatment by inhibiting where our one and that of course is a very.
Port clinical problem in the lung cancer Arena right now.
Yeah.
Yes, that's very helpful. Thank you and maybe the last one on the breast cancer study, so a false positive or Inaki NBC all of her two negative breast cancer, how do you think about the cadence.
Changing landscape with recent progress made by ADP and any insight you can provide on your development strategy.
Well, thank you very so so.
In breast cancer the the work.
The clinical work that's been done so far has been through investigator sponsored studies.
We have noted.
That that landscape is becoming increasingly complicated.
Now Thats fantastic news for patients with breast cancer, but it makes it a a complicated arena for a small company.
And we're also aware that breast cancer trials would have to be quite large and long in duration and so.
Youll notice that when we.
That when we are.
Stating that we are emphasizing hematologic malignancies in prostate cancer that.
Breast cancer is no longer on the list as one of our prioritized indications.
Got it that makes sense. Thanks for taking my question.
Thank you for the good questions.
Thank you. Our next question is from Robert Burns with H C. Wainwright. Please go ahead.
Hey, guys. Thanks for taking my questions and congrats on the updates.
I've got three if I may so with regard to <unk> 301, specifically announced say I'm sort of curious to hear your thoughts around what you think the delta would have to be for accelerated approval between those two arms ibrutinib plus zillow versus ibrutinib, plus placebo any any thoughts around that.
Celine.
Yes.
So we have actually our suspicion looked into this very carefully and.
We have a very.
Statistical significant delta.
I think we.
We can say it could be.
You know anywhere additional.
60, or 70% of what you see in the control arm.
Okay.
Our next question with regarding the sale of 302, obviously, that's an open label Companion study how are you thinking about that potential study or for potential movement into that space. The post progression on ibrutinib.
Yes. So we do go ahead, sorry, Jim.
So actually as you know those patient population have a huge unmet medical need and we believe any.
Any response, if you will be able to rescue those patients.
It could be very meaningful, especially up to Brexit I think obeche Kelly.
Okay.
Last one for me with regard to either way. So I know you have been doing the IND submission.
By the Middle of this year and then you are planning a phase one trial, which is predominant gonna be in Hematological malignancies, but I would assume that you would the next step would then be solid tumors, but can you provide some clarity around sort of timing. When do you think you might initiate our solid tumor program and whether you would institute a biomarker sort of thresholds with regard to raw.
On expression and what that sort of cut off could potentially look like.
Yes.
You squeezed in three questions there in your territory.
So so.
So so we will.
We will investigate.
Solid tumor indications with with the <unk>.
System, but as you know it is a straightforward autologous car T with with.
The same features as successful CD 19 car T, but it doesn't have any enhanced.
Features that would.
Make it particularly applicable to solid tumors.
This is <unk>.
We believe that to move into the solid tumor space that.
Something in addition to the the vanilla car T is necessary and so we're looking in parallel at adding additional features to the platform, but at the same time, we are looking at off the shelf.
Alternatives, such as pluripotent stem cell based car T or car NK.
And in those cases from the beginning we're looking at incorporating additional features into the cell therapy that would be designed to give us a better chance in the solid tumor.
<unk>.
Awesome. Thanks, So theres update guys.
Alright, Thank you Robert.
Thank you. Our last question is from larger commodity <unk> with Brookline capital markets. Please go ahead.
Hi, I'm <unk>, calling in for Kumar Thanks for the update.
With regards to the Owen on Slide 34 program in prostate cancer.
Plan to also test the drug in other indications like airports skin and breast cancer and non oncology indications that <unk> per share.
Also in addition to the IND, enabling studies, what can you share more about the program.
Yes. Thank you. Thank you for the question and give our best to Kumar.
I'm sure he's having a busy day.
Yep. Thank you okay. Thank you so <unk>.
So we.
We do have some interesting.
Indications that the way that 534 inhibits the androgen receptor might be applicable in a non oncology indication called Kennedy's disease, which is a severe form of neuro.
Neuro muscular degeneration, that's related to aberrations in the androgen receptor.
And Andy.
The what I can what I can say about the rest of the preclinical program is that it's moving along very nicely.
Have a formulation identified.
<unk>.
Just gearing up right now to start to toxicology studies.
The the behavior of the <unk> III <unk> molecule up to this point is what we what we would hope to see for a successful small molecule early development program.
Thank you that is useful.
What is the expectation of the safety and side effect profile of on site. When you compare it to say hormone therapies that decrease 9% levels or block androgen action in prostate cancer.
So so.
Since we haven't done.
<unk> toxicology studies yet.
This is a theoretical answer but I would say our first.
Assumption would be that many of the toxicities would be similar to a drug like <unk>.
One there's one thing that we're excited about and that is that some of the androgen antagonists have been associated with seizure activity as a side effect and we were delighted to find that on client III four does not cross the blood brain barrier.
So we have a theoretical possibility of having a lower seizure risk.
Okay great.
And finally I was just wondering if you could speak on the research collaboration the ongoing collaboration with Karolinska Institute.
For these cell therapies.
When can we expect updates on that front.
Okay.
Thank you.
Please.
The collaboration is going well in fact.
We're having two of our collaborators.
Our traveling all the way from Sweden to San Diego next week, and we're going to have our first face to face meeting with them in a year and a half looking.
Looking forward to it and so so the Karolinska of course is where the natural killer cell was discovered in a lot of it's early.
The characterization was done.
And there is a very exciting consortium of companies and academic organizations that collaborate together through the karolinska.
Hi, Ed to make advances in cell therapy, and we were delighted with that.
Im turnaround was invited to join into that consortium. So I think that you can expect to see.
Results from the 534 preclinical program.
At some point over the course of this year as it is on track for an IND.
In mid year.
Great. Thanks for taking my questions.
Alright.
Thank you.
And gentlemen, we have reached the end of the question and answer session.
And I would like to turn the call back to Doctor bike miles for closing remarks.
And let me close by thanking all of you for your time and attention, we particularly appreciate the excellent questions and the opportunity to interact.
The question is on the call today so.
Thank all of you and we look forward to updating you again in about a quarter.
Thank you. This concludes today's conference you may disconnect your lines at this time.
Thank you for your participation.