Q2 2022 Oncternal Therapeutics Inc Earnings Call
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Greetings and welcome to the alternate Therapeutics, Inc. Second quarter 2022 financial results call at.
At this time all participants are in a listen only mode. A 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. Please note. This conference is being recorded I would now.
Now I'll turn the conference over to your host Richard Vincent CFO you may begin.
Thank you Kyle good afternoon, everyone and thank you for joining us today.
Joining me on the call. This afternoon are our president and CEO , Dr. James Reitmeier, and our CMO, Dr saline yards cheap.
Today's call includes a business update and discussion of our 2022 second quarter 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 long tunnels website for at least the next 30 days.
Our 10-Q for the second quarter 2022, it's also available today.
Please note that certain information discussed on today's call is covered under the safe Harbor provisions 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 Zillow 301 study to support a BLA submission.
Timing of a planned interim data updates and the timing of our regulatory filings and submissions, including our R&D submission Franck.
Right.
Our actual results could differ materially from those stated or implied by these forward looking statements due to risks and uncertainties associated with our peers.
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 August 9th 2022, we undertake no obligation to revise or update any forward looking statements to reflect events or circumstances occurring after the date of this call.
With that it is my pleasure to hand, the call over to our CEO Dr. Jim Brian .
Thank you rich and good afternoon, everyone and thank terminal, we are advancing our focused and robust product pipeline with clinical and preclinical product candidates that target cancer for patients with unmet medical needs.
During the second quarter of 2022, we made significant progress across our entire pipeline, including an encouraging data update at Ash go for my Phase one two study of <unk> plus ibrutinib in patients with Mcl in CLO, which Seth.
Hi, Richard It looks like Doctor Brent Maya disconnected.
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Yes.
Thank you.
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I apologize everybody.
Been experienced.
Technical problems on our hometown.
So I was saying that we were especially encouraged by our interim data from patients with P. 53, mutated CLO that we presented at ash.
This is a challenging population to treat with current standard of care PTK inhibitor monotherapy and the combination of Zillow Virtu map plus ibrutinib showed very robust progression free survival.
Also in support of our upcoming Phase III studies zero 301, we entered into a clinical trial collaboration.
By agreement with Pharmacyclics, and Abbvie company, where they.
Great just gracious donation of Ibrutinib to support our global Registrational program. This is an important milestone, which further validates the clinical value testing ibrutinib with zero Virtu map.
Next.
Eight O eight.
<unk> car T therapy product candidate targeting <unk>. One also continued to advance and is on track for an IND filing this month.
We are enjoying strong collaborations with our partners, which include the Dana Farber cancer Institute selling manipulation core facility, along with Lindsay Jen and Mil <unk> biotech.
On the allogeneic off the shelf front, our research collaborations with cellular already and the Karolinska Institute continued to generate encouraging data for our next generation <unk> based cell therapies.
Hi.
$5 three or <unk>.
Lead candidate for the dual action androgen receptor inhibitor or diary programs continued to advance towards an IND filing.
And we expect to have pre IMD interactions with the FDA in the fourth quarter of this year.
We are optimistic that <unk> III for maybe a differentiated and novel treatment alternative for patients with advanced prostate cancer as we believe it interacts with both the end terminal and the ligand binding domains of the androgen receptor inhibitor isn't going to function and inducing its degradation.
Preclinical data have shown that <unk> four exert anti tumor activity in clinically relevant treatment resistant prostate cancer models, including those with AAR amplification.
<unk> resistant or expressing androgen receptor supply experience such as ARV, seven all of which represent significant medical unmet needs for patients with prostate cancer.
This broad advancement of our pipeline has occurred against the backdrop of a focus.
Ken.
Resource cash management approach.
Now, let me turn the call over to Arndt turnover CMO Selim <unk> to discuss our <unk> clinical data and phase III plans in more detail.
Okay.
Yes.
Thank you Jim.
Good afternoon.
As Jim mentioned, we recently presented very encouraging data from our ongoing phase one two clinical trial of Zillow hurt to map in combination with the bridging it at <unk>.
<unk> meeting in June .
And overall response rate of 85% and the CRA is a 41% for patients with mcl treated with Zillow group to map lesser bridge on it which compared favorably to the historical overall response rate of 66% and the CR rate of 20% for Ibrutinib monotherapy.
Median PFS of $35 nine months for Mcl patients with a median follow up of $15. One months, which is also compares favorably to the historical PFS of 12 eight months for Ibrutinib monotherapy.
For patients with <unk> mutation. The median PFS was $17 three months, which is compared again favorably to historical abridged Nib median PFS.
Four months.
In patients with B 53, more cases CLO.
Mark PFS of Zillow bottom up lots of bridging it was 124 months and the 100% at 30 months, which compares favorably to the historical abridging monotherapy landmark PFS around 68% and around 55% at 24 months and months risks.
<unk>.
Okay.
As you May know, what Jason and <unk>.
<unk> three protein is there was no negative prognostic factor in many types of cancer, causing genomic instability and loss of tumor suppression.
The combination of spillover to map.
To be well.
Tolerated was the safety profile, consistent with or slightly improved compared to historical data for Ibrutinib monotherapy.
Example, in patients with Mcl greatly in core neutral fuel decrease was documented in only nine 1% of the patients with Zillow bottom up lesser Britain compared to 29% for Ibrutinib alone from Registrational study.
In terms of upcoming phase III.
That is below 301, we are on track to initiate.
The study later this quarter as we are currently completing key ramp up activities, including site selection and IRB submissions.
As a reminder, zillow 301 will identify patients with relapsed refractory mcl, who have only had stable disease or partial response after receiving four months of Ibrutinib monotherapy.
Randomize them to receive either blinded below book to map or placebo plus ibrutinib.
This study may provide two potential approvals.
First an escalated accelerated approval based on overall response rate.
Overall.
Duration of response.
And second FDA.
MBA approval based on progression free survival or PFS.
Which is the primary endpoint.
Additionally, we are planning to conduct reload three O. Two an open label companion study of Zillow virtue map plus ibrutinib for patients who have progression progressive disease during the Ibrutinib monotherapy.
As of the third.
Yeah.
Of the study.
Zillow two <unk>.
And the result of this study could potentially support an additional approval and indication expansion.
Regarding.
The lead candidate for our I'll call. It gets rolled one targeting car T program. We are on track to submit our IND later this month.
And now what.
Our initial phase one study we plan to enroll patients with relapsed refractory aggressive lymphomas, including patients who have failed CD 19 car T cell therapy.
I will turn the call over to our CFO Rich Vincent to review, our financial results and upcoming milestones.
Thank you Celine are.
Our revenue was to run right from the California Institute for regenerative Medicine, or CERN Grant Sub award and to research and development grants from the National Institutes of health or NIH.
In October 2017, some awarded an $18 $3 million grant to researchers at the UC San Diego School of Medicine.
Our phase <unk> study.
One.
We have conducted the study in collaboration with UC, San Diego and expect to receive $14 $6 million in development milestones under our research sub awards throughout the award period, which was substantially completed from a revenue perspective 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 2 million to support preclinical activities for the company's Oct $5 34 in August 2016 programs.
Our grant revenue for the second quarter ended June 32022 was <unk> 2 million.
Our total operating expenses for the second quarter ended June 32022 was $12 million includes.
Including $1 7 million and noncash stock based compensation expense.
Research and development expenses totaled $8 8 million and general and administrative expenses totaled $3 2 million.
Net loss for the second quarter was $11 7 million or a loss of 23 per share basic and diluted.
Cash flows from financing activities include our first use of the at the market program with Jefferies LLC as our sales agent <unk>.
Through June 32022, the company sold two 7 million shares of common stock for net proceeds of $3 9 million.
As of June 32022, we had $78 9 million in cash and cash equivalents and no debt.
We believe these funds will be sufficient to support our planned operating activities into the first half of 2024.
We have and will continue to manage our cash and all other resources deliberately.
As of June 32022, we had $52 2 million shares of common stock outstanding.
To summarize our upcoming milestones.
For our Zillow burden that program, we expect to initiate the global Registrational Phase III study Zillow 301 in September 2022, and provide an interim clinical data update from our phase <unk> study of <unk> plus ibrutinib in patients with Mcl and CLO in the fourth quarter of 2022.
Yeah.
Frank <unk>, our lead autologous <unk> car T cell therapy candidate, we plan to submit our first <unk> in August 2022.
<unk> $5 30 for our lead product candidate, we expect to have interactions with the U S. FDA in the fourth quarter of 2022.
With that I will turn the call back over to Jim.
Thank you rich.
<unk> has performed well in this historically challenging macro environment, we plan to continue to use our capital and resources efficiently as we advance our focused pipeline towards significant value inflection points that we believe will make a difference for patients suffering from hematologic malignancies and prostate cancer.
We look forward to events later this quarter, especially the planned initiation of our global Phase III <unk> study and also submitting our ROI on car T IND application as well as advancing our diary program towards the clinic.
Thank you for joining us today, and we look forward to updating you over over the year and half conferences with that I will turn things back to Kyle for the Q&A portion of this afternoon's call.
Thank you at this time, we will be conducting a question and answer session. If you'd 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'd 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, one moment, please while we poll for questions.
Our first question is from <unk> Singh with Oppenheimer. Please proceed with your question.
Great. Thanks, everyone.
The update.
Question.
It's great to see all the programs moving ahead.
Just on the interim update.
Jim and team.
Looking at the PPP mutated PLL patients.
You saw some pretty good.
Maybe you can call high opening data with the PFS that 36 month or a 100%.
What are your thoughts on <unk>, what are the sort of discussions you could have with regulatory authorities on that is it that you could run a trial just Darren was communicated patients lobby.
Easy to find in a clinical trial put on clinical trials, just any fault there.
And then secondly can you just speak a little bit more into what's your phase one two will look like with the with the one 808 car T.
Is it a basket trial focused on.
Patients.
2019, sorry, if you can just kind of dig into that a little bit more. Thank you for the question.
Sure.
Thank you. Thank you for the good questions and so I'll answer the first one Celine.
Selim can handle the second one so so we do believe that the.
Very.
Pleasantly surprising.
Strong PFS results up a 100% for patients with <unk> three mutated CLO.
<unk> is a does represent an opportunity for a registration strategy.
We believe that about 50% of patients with CLO carry one of these abnormalities, which can include both mutated P 53 sequences, but also deletion of the P 53 gene or portions of the chromosome and so.
Most patients are already typed for that.
It's known to be challenging.
Characteristic for TK inhibitor treatment and so we think that it would be.
We think we think there is a potential there for for an additional registration strategy.
We're headed back to the bench to try to figure out what what is going on between <unk>, one and <unk> 53, we know there's got to be some interesting science. There. So we hope to learn more about that in the near future.
And so that's your first question and let Selim talk about the phase one study for <unk> our car T.
Yes, Thanks, Jim.
Yes, hi.
What we're planning to do here is to have a.
Aggressive lymphoma in our dose escalation phase.
<unk>, which is specifically is going to be diffused large b cell lymphoma and.
Mcl.
Once we reach our.
Our recommended phase two dose we can expand.
And those two indication and we May go into.
Possibly into additional Hematological indications.
Great. Thanks, and just a quick follow up.
Jim can you just put any kind of.
Idea on the timing.
Go back to bench.
Understand the science behind it is the people GTO abdomen abnormalities and then when would you go and talk to regulators I mean can you just talk about 2023 about maybe 2024, just any thoughts there.
Just in terms of just the patients you are talking about.
Are there any limitations just following your manufacturing site that you choose for the 201 car T study thats all the questions.
So I think I can get both of those.
And so.
First for you were asking about.
About the manufacturing side of the car T program is that right.
Oh, yes, yes, yes.
Yes.
Okay and so we are we've got.
We're having a delightful collaboration.
With the cell processing facility at the Dana Farber actually some some involving some people who I've known for decades, and they've got they have a vast amount of experience with the prodigy cell processing system that we're using that we think is going to be.
Ground breaking in the cell therapy field with a really different manufacturing model and so we are.
We're working out all the logistics right now, but we think it's going to be pretty straightforward to get to get the patient cells to Boston.
Then their car T product is frozen and can be transported back for infusion.
Both both ends of the supply chain are pretty straightforward.
And then I think timing wise, where.
As you know we are being very careful with our cash reserves right now.
And so the.
We won't be opening a CLO study.
This year, certainly probably not next year, but we're hoping to have some science to talk about really as soon as we can generate it I will say that a.
New a new indication.
Could be.
The game changing for 50% of CLO patients is something that.
Some some strategic.
Pharmaceutical companies are interested in.
Okay, great. Thank you Jim Thanks for all the all the answers on the call.
Thank you Josh.
Our next question is from Carl Byrnes with Northland Capital markets. Please proceed with your question.
Congratulations on all your progress and thanks for the question. My question is on the <unk> three mutation were answered so I'll move on to a couple of others.
I'm wondering if you have any visibility into the timeline of data from the phase <unk> investigator sponsored trial at UCSD and prostate cancer and then also considering the IND submission in August for eight O. Eight would you expect the timeline for first dose patient to be in the September ish area.
So first I'll start on the investigator sponsored study, we really don't have any control over the rate of enrollment or availability of data. So I can.
We know as much as you do Carl you, usually no more than we do but I'll, let I'll, let <unk> comment on the second question.
Yes can you. Please report repeat your second question. Please.
Yes. This is with respect to 808.
<unk> is going to be filed in August would it be safe to assume or would your expectation be the first patient dose would be in the September timeframe.
Or whatever timeframe you would expect.
Well I mean, as you know we're going to submit the IND.
And it will probably be 30 days hold on periods from the FDA. So.
Before we get the Green light that Theres no questions from the FDA, that's probably going to put us until end of September beginning of October .
And I think with regard to the patients.
Once we get the.
IRB approval and it may take some time, it's going to be.
Ready to go but we are hoping to have our patients hopefully by before the end of this year.
Great. Thank you.
Thank you Carl.
Our next question is from Robert Burns with H C. Wainwright. Please proceed with your question.
Thanks for taking my questions.
If I may.
So I know that youre going to be pursuing CD 19.
Patients who received prior to COVID-19 targeted therapy.
Great. Thank you. Thanks, a lot for your ROE on targeted car T. I was just curious whether youre also thinking about solid tumors given the expression of more than one in solid tumors, such as breast lung and stomach cancer.
And then my second question.
Your financial guidance for your operational runway does that take into account clinical trials for both <unk> and your lead asset.
So I'll I'll answer I'll answer the first question and then we'll have rich talk to you about the cash runway. So so.
Yes, we are we're very interested in extending our cellular immunotherapy program in <unk>.
Two patients with solid tumors.
As you know very well.
The current generation of car T.
Even though they work so very well in liquid tumors have had a hard time overcoming the immuno suppressive microenvironment of solid tumors and so.
I think that most people in the field feel like we do that youre going to need some additional success factor.
To get somewhere with the solid tumors like checkpoint inhibition or.
TGF beta suppression something those are those are the sorts of things that people are looking at and so we're keeping our eyes open for potential add on therapy to the car T that would open up the solid tumor tumor field.
We we could treat some solid tumor patients can have kind of a basket trial.
Without that technology, but we think that it would be more likely to succeed with additional tech.
And rich on the runway question.
Sure. So overall our model or spend forecast does include what we've discussed today in our upcoming milestones and it also includes the initial studies for both <unk> and <unk> to $5 34 in this time horizon.
Awesome. Thanks, guys.
Rich and I have always been very thrifty, and we're going to stay that way.
Yes.
Okay.
Our next question is from Kumar Roger with Brookline Capital markets. Please proceed with your question.
Thanks for taking my questions and also congratulations on the progress.
With regard to Honked eight eight.
What are your expectation in terms of the starting dose and how soon do you think you can get to the recommended phase II dose.
Yes Kumar Thank you and thank you for the question.
Going to start at a dose of one times 10 to the sixth T cells per kilogram of ideal body weight and that is a that's a starting dose that FDA already agreed we could use in pre IND discussions and we thank them.
That we can get to a recommended dose with <unk>.
Three.
Maybe maybe four but just a few dose levels, we think we'll be able to get there pretty quickly.
Okay and.
You will have sales from like a single manufacturing runs to do all these dose escalations.
Yes, we are.
Getting with healthy donor Luca packs were getting massive numbers of car T cells with very high expression levels and so we can we can make and we.
Appear to be able to make more car T. Cells. Then we've been then we're going to need.
Okay.
And with regard to the cleaning kind of lagged remained with Pharmacyclics supplemental.
The broadening.
How much involvement will they have an <unk>.
Clinical trials, finding what kind of.
Expectations are built from <unk> doesn't matter for this.
So.
We're having we're enjoying a really.
Good working relationships with the Pharmacyclics and Abbvie clinical team they have provided.
Some some very helpful advice in terms of.
The study design and some elements their experience with Ibrutinib as is.
It is very <unk>.
<unk> here and so.
They have.
If if we make changes in the protocol, we would welcome their assistance with with any modifications that we make.
But I think to be clear.
Don't have any.
Commercial rights to the product gained from this relationship.
Finally with regard to 534 following the pre owned interactions with the FDA. What do you think would be the timing of Diana <unk> filing part of that.
So filling amount I'll take this on me because of the preclinical question Theres, an interesting COVID-19 related thing going on right now and you may have heard this from some of the other companies that you follow but there is a worldwide shortage of Beagle.
<unk> four.
Preclinical toxicology work and it's going to take some time for <unk>.
Believe it or not for the dog supply to catch up with the demand and thats. The species that everybody uses for Tox studies and so so.
We're in a little bit of a holding pattern right now for the timing of finishing our tox work.
We are confident that we'll have an IND next year, but we're not guiding to a date at this point.
Great. Thanks, so much.
Alright.
We have reached the end of the question and answer session and I will now turn the call over to CEO , Jim Bright Meier for closing remarks.
So thank you everybody for joining us today, and we were pleased to pass along our significant progress and delighted to be able to interact with such good questions with those who are following the company and so with that thank you.
You and good day to everyone.
This concludes today's conference and you may disconnect. Your lines at this time. Thank you for your participation.
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