Q2 2023 Onconova Therapeutics Inc Earnings Call
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Ladies and gentlemen, thank you for standing by.
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Welcome to the <unk> okay.
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So both therapy decks.
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Thank you, let me restart ladies and gentlemen, thank you for standing by welcome to the Encore, Nova Therapeutics second quarter 2023 financial results and business update conference call. At this time, all participants are in a listen only mode.
Boeing managements prepared remarks, we will hold a question and answer session to ask a question at that time. Please press star followed by one on your Touchtone phone. If anyone has difficulty hearing the conference. Please press star zero for operator assistance as a reminder, this call is being recorded today August 10 2023.
At this time I would like to turn the call over to Bruce Michael of lifestyle Advisors go ahead.
Yes.
Thank you operator, and welcome everyone to Orca Nova's second quarter 2023 financial results and business update conference call.
Earlier this afternoon on canola issued a press release reporting its financial results and business progress.
If you have not yet seen this press release it is available in the investors and media section of the Companys website at Www <unk>.
Dot com.
Following my introduction, we will hear from <unk>, President and CEO , Dr. Steve Fruchtman consulting Chief Medical Officer, Dr. Victor <unk>, and Chief operating Officer, and Chief Financial Officer, Mark Guerin.
Hakan <unk> as VP of regulatory affairs, and quality assurance Fred Furlough will also be available during the Q&A session. Following their prepared remarks.
Before we begin I would like to remind everyone that statements made during this conference call will include forward looking statements under the Safe Harbor provisions of the private Securities Litigation Reform Act of 1995, which involves risks and uncertainties that can cause actual results to differ materially.
We're looking statements speak only as of the date. They are made as the underlying facts and circumstances may change, except as required by law.
<unk> disclaims any obligation to update these forward looking statements to reflect future information events or circumstances.
For more information on forward looking statements. Please review the disclaimer in today's press release and the risk factors in the company's SEC filings.
With that I will now turn the call over to <unk>, President and CEO , Dr. Steve Fruchtman.
Okay.
Thank you Bruce and thanks to all our investors and analysts who are listening today.
As you know I can know really dedicated to developing novel differentiated therapies.
<unk> with Kashi.
That app by targeting.
The most important pathways that enable cancer cells.
We are very encouraged about the outlook.
For our two lead programs.
Involving neurology cyclic a differentiated multi client HDD CDK four six inhibitor <unk>.
<unk> proteins involved in resistance pathways and.
And Regal assertive.
Cell signaling inhibitor.
Over the last quarter.
Worked diligently to advance the development of both programs and multiple company.
Investigator sponsored phase, one and phase II trials.
Data from these studies.
The clinical and regulatory strategy for each product candidates.
Over the course of the quarter.
Also presented encouraging preclinical data on each program at several very prestigious medical meetings, including <unk>.
The ACR ash meetings.
Presentation of these data confirms the value proposition for <unk>.
<unk> Cyclin E survey and recognition.
A rigorous pre clinical and clinical.
Hi, Tiffany community warranty data from these important presentation.
In addition, we opened an important and constructive dialogue.
The FDA.
Related to the requirements for a regulatory path for Regus Sir.
For an approval in the ultra rare indication of IDM associated squamous cell carcinoma.
Looking ahead to the rest of 'twenty <unk> three.
And early 'twenty 'twenty four.
<unk> web.
We will be focused on defining the mono therapy.
<unk> phase II dose and advancing the program into one or more randomized studies.
Read assertive.
We will be focused on mapping out a registrational study plan to discuss with the agency are Deb associated squamous cell carcinoma.
Based on the very impressive clinical responses.
That had been seen in previously refractory patients.
And presented at major medical meetings.
We also continue to support the ongoing investigator sponsored and checkpoint inhibitor combination studies.
With me are assertive in K, Ras mutated non small cell lung cancer and advanced malignant melanoma.
Importantly.
K Ras mutation in non small cell lung cancer.
Ligand melanoma.
Importantly, <unk> non small cell lung cancer and advanced.
Lung cancer trial welcomes refractory patients with any K Ras mutation.
And the clinical data support our hypothesis that.
Responses should be seeing will matter K Ras mutation Chris.
And in fact responses are now reported and appeared to be chaos agnostic to the effects of regressed.
In combination with all the math.
Before we dive into the details for each program.
I would like to introduce to you argued consulting Chief Medical Officer, Dr. Victor Mohawk.
It isn't on the assets, you're fine global health professional position and successful clinical researcher Joanna can know.
And the untimely passing of.
Our late Chief Medical Officer, Dr. Marc Gallagher.
And the extraordinary service of our interim Chief Medical Officer, Dr. Michael Saunders.
We thank Michael for his service to our de Nova and to the patients with advanced cancers entering our trials.
His leadership.
Mike will remain as a consultant to the company.
Victory has hit the ground running and is already making an important contribution to <unk> clinical development efforts.
Victor brings a great depth of experience.
From his three decades of work in clinical research.
<unk> more than 15 years.
In the biotech industry.
He has held responsible leadership roles and lead programs at the center core.
Biotech subsidiary of J&J.
Merrimack pharmaceuticals, as well as other emerging start ups.
I personally have known Victor for more than 15 years working with him. When we were together at ortho biotech and he was leading the erythropoietin Alpha trial in Myelodysplastic syndrome, as well as the docs will trial in advanced ovarian cancer.
Obviously both of these drugs are approved and Erythropoietin also was a multibillion dollar franchise for lots of biotech.
It is with great confidence.
And re welcome Victor warmly to the Ogden over King.
For our update today, we will focus primarily on two topics.
Starting with our CDK four six inhibitor <unk> cyclin.
The first topic will be the progress.
Our efforts to define a recommended phase II dose.
<unk>.
Worldwide sales of the top six drugs in this class top $6 billion in 'twenty 'twenty driven by the ability to improve.
Regression free survival.
We believe that <unk> has the potential to be.
A differentiated enchants entrant into this market.
Based on an improved safety profile.
Importantly, the low risk.
Shipment of resistance.
But totally target targeting proteins.
Wow.
These resistant pathways.
Our efforts over the last year have been dedicated to completing a phase one program.
Defining the recommended phase two dose to support evaluation of a combination trial with <unk> naturally gel with Registrational intent.
The clinical program includes two phase one monotherapy studies in patients with solid tumors and one phase one slash two dose escalation trial in <unk>.
The nation with Letrozole in patients with low grade endometrial endometrial cancer.
Also known as Al G E C.
Patients continued to be entered onto the trial and we anticipate reporting top line results from these studies.
<unk> safety.
Pharmacology and selection of a recommended phase two dose in the fourth quarter of this year.
We will use this information to define and initiate additional combination studies in other indications once the dose is identified.
Based on the progress seen to date.
We anticipate initiating.
Randomized trial and LG you see in the first half of 'twenty 'twenty four.
Moving on to Riga asserted.
Second topic will be related to the development of a registrational path for Wingo service.
As you May know, we had a type b meeting with the FDA towards the end of June .
Based on this constructive meeting and feedback from the agency and the impressive clinical responses in these previously refractory patients with a tremendous unmet medical need.
We have seen and presented at major medical meetings, our clinical data.
We intend to develop a protocol for a potential registrational trial with <unk> in patients with <unk> associated squamous cell carcinoma.
We will provide an update on next steps in the first half of 2024.
With that overview and introduction I'll invite Victor to give you more insight and take you through the latest updates on bulk neuralgia cycling and regrow Sheridan.
Sure.
Thanks for the introduction Steve.
I'm very excited to join on canola and believe that our two assets have the potential to improve the care of people with cancer.
So I'll start by providing you with an update too on that RASM cyclists.
We believe that matter I wouldn't think there's the potential to improve even more than other CDK four six in <unk> because of its unique attributes.
Number one <unk> differentiated safety profile with potentially less mindless oppression neutropenia than they are.
Other drugs in this class.
Number two we have already demonstrated.
And feel confident that <unk> can be administered once daily.
And every day.
Thus there is no need for a drug holiday to permit bone marrow recaps battery.
That is required by the C. D. Four 6K in <unk>, and which May tell me its reputation of cancer cells.
Number three.
It inhibits multiple kinds of things.
This activity could contribute to enhanced tumor growth inhibition and overcome immune suppression in the tumor micro environment.
And does this.
This fall becomes.
Development of treatment resistance.
During our first quarter call, we reported observations from the phase one study of patients with solid tumors that indicated that it's a continuous daily dosing schedule of 240 milligrams.
The site achieved target engagement with an acceptable safety profile.
We also reported the initiation of the first phase one two study evaluating the combination of <unk> and letrozole in patients with recurrent low grade endometrial endometrial cancer, abbreviated LG E C.
And we reported positive preclinical data at AAC.
1023.
<unk> demonstrated that narrows the fact it can be.
In fact at least Synergistically combine with other agents and additional indications.
So we believe <unk> is an ideal first indication for <unk> sake.
Comparing the data suggests that off label combination use of CDK <unk> inhibitor and Letrozole improved progression free survival in recurrent LG.
However, these regimens tia to be negatively impacted by issues of safety tolerability and treatment resistance, creating an unmet need.
The need for new therapies.
In addition, beyond inhibiting CDK four six <unk> uniquely targets a protein Nicole Bob one.
Oh, but expression of Bob one is linked to poor outcomes in tumors, including breast and endometrial cancer.
Together, the content data and Bob one action.
The potential for <unk> to make a positive impact on LG <unk> and other indications.
Looking into 2024, we intend to begin at least one additional combinations that you have narrowed the effective and letrozole in a different indication.
And we will provide additional details once a clinical protocol is finalized.
Next I'd like to speak about our plans to define a registrational path for <unk>.
We have been evaluating the clinical potential for this compound is a single agent in the ultra.
Lead indication of our Deb associated squamous cell carcinoma, and separating in combination with checkpoint inhibitors.
During our first quarter call, we reported on data presented at the I S. I D.
D.
International Society of investigative dermatology and <unk>.
International <unk>, <unk> symposium showing that patients with refractory.
Our Deb associated squamous cell carcinoma achieved complete cutaneous clinical responses of all the cancer its leash skin lesions.
We also observed that patients treated with either IV or oral <unk> experienced durable responses and that <unk> had been well tolerated with no additional toxicity in this new important indication.
The enormous interest from the international experts in the disease supports our enthusiasm to continue to develop <unk> for this indication.
I'll point out that our Deb associated squamous cell carcinoma is a very high mortality and there are no effective therapeutic options.
Patients with a dip could develop the Sps squamous cell carcinoma hit that 50% mortality within two and a half.
Yes.
And this is the most common cause of death in these patients.
Because of this high and urgent unmet need we requested and completed it type B meeting with FDA in June .
As Steve mentioned, the meeting was constructive and based on our discussion our goal is to develop a protocol for a registrational trial.
And discuss this strategy with F D a.
And their review.
Notably <unk> result in Dib associated squamous cell carcinoma may have positive read through into more prevalent indications.
A key driver of the disease.
<unk> one <unk>.
That is all the expressed in other cancers and Potently inhibited by <unk>.
We continue to collaborate Pangea biomet, an AI company to identify biomarkers that could predict response to request it.
In addition, we continue to evaluate the potential to combine <unk> in combination with checkpoint inhibitors through two investigational sponsored studies or I S. T.
The fifth <unk> is being conducted by investigators at the <unk> School of Medicine at Mount Sinai In New York.
Sure.
This phase one two studies evaluating the combination of <unk>.
And the volume up in patients with K, Ras mutated non small cell lung cancer.
Have failed prior therapy with a PD one checkpoint inhibitor.
As reported last quarter based on encouraging efficacy data index septuple safety data there.
Protocol was amended to.
Allow said that dose escalation of renegotiated.
Patient accrual is intended to be complete at the end of the year.
We would expect the investigators to provide an update of the trial in 2024.
The second thing is to ISG is being conducted at Vanderbilt University and initiated enrollment in may.
This same on stage two stage design is evaluating <unk> in combination with keytruda in patients with refractory metastatic <unk>.
Melanoma.
And with that ill.
Conclude my portion of the call and hand, it off to Mark.
Thank you Victor.
<unk>, the second quarter of 2023 with cash and cash equivalents of $29 7 million.
Compared to $38 8 million as of December 31, 2022.
Based on our current projections, we believe that our cash position will be sufficient to fund our ongoing clinical trials and business into the second quarter of 2024.
Research and development expenses for the second quarter of 2023 were $2 5 million compared to $2 million for the same period in 2022.
General and administrative expenses for the second quarter of 2023 were $2 2 million as compared with $2 1 million for the same period in 2022.
Net loss for the second quarter of 2023 was $4 3 million or <unk> 20 per share on 21 million weighted shares outstanding.
That compares with a net loss for the second quarter of 2022 of $4 million or <unk> 19 per share on 29 million weighted shares outstanding.
The increase in net loss for the second quarter of 2003, compared with 2022 was primarily a result of the cyclic clinical development and manufacturing expenses in the 2023 period.
With my financial overview complete I'll now hand, the call back to Steve for his concluding remarks.
Thanks to both Mark and vectors for that review.
In conclusion.
We are very optimistic about the outlook.
Our two lead compounds.
The promising clinical observations safety signals.
Supporting preclinical data along with our strategy.
For eventual health authority approval.
Compounds.
For <unk>, we believe this CDK for US this compound has the potential to provide differentiated efficacy and safety.
Reduced bone marrow toxicity.
<unk> kinase inhibition padded.
And then improved administration scheme.
To date, we have seen target engagement and the development of mild.
Which permits a once per day dosing regimen with.
Without the need for a drug holiday that permits bone marrow recovery, but may also permit cancer cells to proliferate.
We expect to report top line results from our phase one mono therapy and phase one slash two combination study with Letrozole in the fourth quarter of this year.
The readout will include safety pharmacokinetics and the definition of a.
The recommended phase II dose.
Looking ahead to 2024.
Plan to advance in their Azure cyclic letrozole combination into a randomized trial in patients with low grade endometrial endometrial cancer in the first half of 2024.
We intend to leverage the results of the preclinical studies presented in the second quarter to define further combination studies with <unk> or other compounds and then additional indications.
For Regal authority.
We continue to believe that <unk> is unique.
Mechanism of action and cell signaling pathways.
Including K Ras mutations.
Combined with an acceptable safety profile could position it as an attractive anti cancer agents.
We had a constructive type b meeting with the FDA.
A discussion of <unk> mono therapy.
Reed ultra rare indication of all that complicated by squamous cell carcinoma.
Based on that meeting we plan to design a registrational trial.
Look to provide an update on next steps after continued dialogue with the agency in the first half of 2024.
In addition, we continue to believe that <unk> added.
The potential to act synergistically with checkpoint inhibitors.
That has response rates and overcome.
<unk> inhibitor resistant.
Randy using an ISG strategy to evaluate this approach.
Two studies, thus underway.
Evaluating rigor assertive with checkpoint inhibitors in patients with melanoma.
K Ras mutated refractory non small cell lung cancer.
While enrollment in the melanoma study started quite recently enrollment in the lung cancer study is expected to be completed at the end of this year and the investigators can provide an update either trial in 2024.
In closing I want to thank our management team employees partners and investigators as.
As well as the brave and dedicated patients who participate in our experimental clinical trials.
And the investment community.
Your support of our efforts to bring new medical entities to patients at Nomura.
We look forward to providing you ongoing updates on the company's progress.
With that.
We will begin today's.
Q&A session.
Operator.
Ladies and gentlemen, if you would like to register for a question in today's question and answer session. You will need to press Star and then the number one on your telephone.
If your question has been answered and you wish to withdraw your request you may do so by pressing.
Star and one again.
If you are using a speakerphone please pick up your handset before entering your request.
One moment please for the first question.
Our first question comes from Charles <unk> with Guggenheim.
Hi, guys. This is Edward on for Charles.
Thank you for taking our questions.
Maybe a first question on the.
There is a cyclic monotherapy dose escalation and I'm just kind of wondering what what remains to be done for you too to establish an RP two D. It sounded like on the past call that you are getting pretty close or you still.
Enrolling patients have you have you cleared another dose cohort just kind of what's the status there and then as a follow up question on the.
Combination with Letrozole for LNG EC just any color there on how recruitment how that trial is going thank you.
So my first question.
We are currently I think we've mentioned this in the past that <unk> 40 milligrams every day.
For these patients that were in the middle of expanding that cohort.
And you know it's hard to predict as you know it depends on the number of D. L cheese.
No additional <unk> seen in the next cohort will be at 280 milligrams.
So we believe we're close spaced.
Target engagement.
One marker that shows us whether that shelves are proliferating a proliferation proliferation marker.
Evidenced it sells.
Not proliferating at this current dose of the RASM cyclin, but we're also seeing mild neutropenia, which we could have expected.
Just on those two observations, we believe we're getting close.
How close is close and sometimes hard to predict how we may be at.
Dose limiting toxicity at 240, <unk> in which case the recommended phase two dose should be 200, all we may ask to expand to another cold water 280 milligrams and we anticipate knowing this in the next few months.
The second question.
Edward was what.
Alright, thanks for that color.
Maybe just on the Letrozole combo, just how how enrollment is going and how that how that any color on the progress on that combination trial.
Right.
That trial is open.
A number of sites across the country, including NYU Mds analysis.
It took a while to get accrual growing we believe we had to amend the trial.
Our eligibility criteria.
Strictly decided because the key thing about this trial is to get the dose of the combination of <unk> cycle, then let resolved so based on the amendment, we believe accruals should increase or we anticipate.
Again.
Before the end of this year, which has always been our prediction.
The combination of the monotherapy trial and the trial, specifically starting elg.
LNG EPC that we will have the recommended phase two dose of the combination of <unk> and Letrozole before the end of this year.
Does that answer your question limit.
Yeah.
Our next question comes from.
Who the mirror.
Ladenburg Thalmann.
Good afternoon. Thank you for taking my question and congrats on the progress in this quarter.
Victor also congrats on taking the full time position that the PMO I have two questions. One on the narrow as the cycle. It could you comment on the Letrozole combinations for endometrial cancer in terms of the safety signals are there any overlapping safety signals and then anything that you could.
Should the highlight for us.
Sure So I'll take that.
We're mostly focused on finishing the mono therapy trial with single agent in there as the cycle now explain to you while it and it has to do exactly with your question.
All of the CDK four six inhibitors combine with anti estrogens.
Currently net resolve progressed Trent and we plan to do that as well and there is no cross taxes.
<unk> toxicity between whereas a cycle of as ACD, a multi kinase CDK four six inhibitor and an anti <unk>.
So we anticipate the combination will be safe and we will have a few patients on the trial, but the key thing will be to show the safety of the combination which will permit us to open a randomized trial in early 2024, so the combination of the monotherapy trial and.
Study, specifically in low grade endometrial cancer with net yourself I think those two studies, which should be finished by the end of this year, which will lead into a randomized trial in low grade endometrial endometrial cancer and that's our goal.
Thank you, Steve and the follow up question would be aimed at solid tumor knows a cyclic trial are there any indications that's dominating the enrollment any particular indications, we'll see more data on.
Okay.
I didn't catch what you're asking about the monotherapy trial and what type of cash as of being put on to that is that your question could you repeat it yes.
That is correct in the solid tumor neither pikelet trial, what indications are you enrolling and also any of the indications that you see more.
More numbers of patients enrolling in the trial that we will see more data from those indications.
So the mono therapy trial is open to all and stage cancers and is very variable. There is no one type of cancer that dominates.
The typical end stage patients. It could include lung cancer prostate cramps in bladder cancer ovarian cancer, So, it's very diffused and Theres no.
Single indication that dominate so I don't think other than safety.
Don't anticipate.
Don't expect to have any efficacy signals can be ah patients are very diverse regarding their indications and their cancers. So the goal like most phase one studies just to establish a recommended phase II dose and I think the endometrial endometrial cash when it's up and running at the same.
Time to combine the recommended phase two dose of monotherapy in there as the cycle with that result, as the kind of the.
Safety of the combination, which I already said, we anticipate will be completely say just like it is with the competing CDK and the approved CDK <unk> inhibitors, and we don't anticipate any toxicity issues. When let yourself is going to be added to the recommended phase II dose.
<unk> generated from the monotherapy trial.
Thank you Steve very helpful.
Our next question comes from.
Joe.
From HC Wainwright.
This is landon on for Joe Thanks for taking our questions I have two questions. The first question <unk> are we expecting any initial efficacy data in the readouts anticipated need for Q.
So I'll take that one so to the CDK four six inhibitors and Thats a great question by the way. These are very important question. So the investment community and the analysts who.
They already understand how these drugs work these are not cytotoxic drugs.
Yes.
Class of drugs prevent tumor proliferation.
And if you look at the.
The approvals for the three health authority approved CDK four six inhibitors. They are all based on two end points.
The first is progression free survival.
And the second is overall survival and the reason for that is because they are not cytotoxic you do not see many responses you may.
Periodically see a response, but it's probably in single digits.
So the way these drugs work to try to improve patients' lives by prolonging PFS.
And longing overall survival and rushed to really evaluate that intelligently.
To control that.
You could use historical controls by all means.
Really in the modern era, the way to do that is with the control arm to show improvement in either PFS or OS and Russ.
<unk> established a recommended phase II trial.
Yes.
Hurdle will be too okay.
Randomized trial in early 2024, and <unk> and that is our plan and we remain on target for that plant.
Got it.
Got it and one more question for <unk> R&D Beach I may have missed it but if you could provide us an update on how many patients are still pending to be enrolled in the phase II trial.
So this is we have.
Two international sites as.
I S. T is participating in this trial.
One at Thomas Jefferson in Philadelphia, We are one of the world's experts in <unk> squamous cell reside Dr. Andrew South and also that your.
I'll hand, Bauer and Austria.
Two primary sites.
Just with the.
The results of these trials have been presented we now have request to treat patients with Israel and Chile in Paris, France.
Doing it on a compassionate use approach.
And in discussions with the agency.
With the agency specifically, they asked us and we will transition their trials towards Aquino response or trial and again because these patients may appear anyway, we may ask to do it as once a patient is identified anywhere in the world because these are ultra rare.
Patients then we would open up a site or perhaps a patient can travel to one of the major medical centers.
Our expert Ardeb squamous cell so.
The responses have been reported at a major medical meeting we have what we think is very impressive cutaneous complete remissions.
A number of patients since those presentations are now also on the trial and the <unk>.
Compassionate use approach I believe there is another patient more recently provided tried at Thomas Jefferson, but those patients are too early for efficacy evaluation, but they continue on either oral or intravenous Riga surgery, and we look forward to the <unk>.
<unk> see.
On the efficacy signal.
Large number of patients in the interim.
And as Jeff just said to create a protocol to go back to the agency and get their buy in on a donkey responsive trial potentially an odd Deb squamous cell carcinoma.
Thanks for clarifying Steven Thank you for the updates.
Pleasure level.
Our next question comes from Robert Leboyer from Noble capital markets.
Okay.
Good afternoon, and my question has to do with the melanoma trial going on at Vanderbilt and I was wondering if you could give any additional details as to the number of patients or the progress thats been made or any particular data points that might be ahead.
So we have not publicly stated how many patients are on that track.
And that the first cohort is enrolling in that first cohort is I believe almost completed.
Maybe a little bit too early to evaluate efficacy there. So it's up to three patients or the next cohort so.
So far Theres been no safety concerns and the next cohort obviously would be at a higher dose of <unk>.
We are sort of in that trial in malignant melanoma is quite early in its progress.
Okay. Thank you very much.
I'm showing no further questions in the queue at this time I'd like to turn the call back to Steve for any closing remarks.
Thank you again, operator, and thank all of you for participating in today's call.
We are pleased to be approaching important milestones as we mentioned across our pipeline and look forward to providing additional updates as they are achieved.
Thanks, again for participating and for your excellent questions and have a wonderful evening. Thank you again.
Yeah.
Yeah.
Thank you all for participating in today's call.
This concludes today's call.
You may now disconnect.
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