Q4 2022 Onconova Therapeutics Inc Earnings Call
Speaker 2: Ladies and gentlemen, thank you for standing by. Welcome to the Anka Nova Therapeutics fourth quarter and full year 2022 financial results and business update conference call.
Speaker 2: At this time, all participants are in a listen-only mode. After making management-prepared remarks, we will hold a question-and-answer session.
Speaker 2: To ask a question at that time, please press star followed by the number one on your touchtone phone. If anyone has any difficulty hearing the conference, please press star zero for operator assistance.
Speaker 2: As a reminder, this call is being recorded today, March 16, 2023.
Speaker 2: At this time, I would like to turn the call over to Bruce Mackle of LifeStuy Advisors.
Speaker 3: Thank you, operator, and welcome everyone to Anka Nova's fourth quarter and full year 2022 financial results and business update conference call.
Speaker 3: Earlier this afternoon, Anka Nova issued a press release reporting its financial results and business progress. If you have not seen this press release, it is available in the investors and media section of the company's website at ankanova.com.
Speaker 3: Following my introduction, we will hear from Anka Novus President and CEO , Dr. Steve Fruchman, Chief Medical Officer, Dr. Mark Gelder, and Chief Operating Officer and Chief Financial Officer, Mark Garan. These prepared remarks will then be followed by a question and answer session.
Speaker 3: Before we begin, I would like to remind everyone that during this conference call, we'll include forward-looking statements under the Safe Harbor provision of the Private Securities Litigation Reform Act of 1995, which involves and uncertainties that can cause actual results to differ materially.
Speaker 3: Forward-looking statements speak only as the date they are made as the underlying facts and circumstances may change Except as required by law Pankanova disclaims any obligation to update these forward-looking statements to reflect future information events or circumstances
Speaker 3: For more information on forward-looking statements, please review the disclaimer in today's press release and the risk factors in the company's FCC filings. With that, I will now turn the call over to Anka Novem's President and CEO , Dr. Steve Fruckman. Anka Novem's President and CEO , Dr. Steve Fruckman
Speaker 4: Thank you, Bruce.
Speaker 4: And thanks to all who have joined the call today.
Speaker 4: We are entering a very exciting time for Anka Nove.
Speaker 4: As our recent progress
Speaker 4: as just moving toward anticipated milestones.
Speaker 4: that we believe.
Speaker 4: will serve as key value inflection points.
Speaker 4: I'll begin today by providing the highlights of this progress.
Speaker 4: before turning the call over to Dr. Mark Gelder, our Chief Medical Officer.
Speaker 4: to elaborate further.
Speaker 4: Let me begin with a discussion of our lead asset, Nrazacyclib.
Speaker 4: Which, as a reminder,
Speaker 4: is a multi-clinase inhibitor.
Speaker 4: targeting CDK for
Speaker 5: About six
Speaker 4: and other kinases important.
Speaker 4: for tumor growth and metastasis.
Speaker 4: We are pursuing neuropsychoskeletal development in multiple cancer indications.
Speaker 4: based on both preclinical and clinical science.
Speaker 4: with estrogen blockade in endometrial cancer is on track to open for enrollment and screening patients later this quarter. In parallel, our phase one trials of single agent neurosocyclib in the US and China have continued to demonstrate the assets favorable safety profile to their fifth dose escalation cohorts.
Speaker 4: Based on these studies, we will be able to place patients on a once daily continuous dosing regimen in endometrial cancer as well as in future studies. Once daily continuous dosing differentiates niragicyclib from each of the three health authority approved DDK46 inhibitors.
Speaker 4: of these agents which are multi-billion dollar franchises
Speaker 4: these agents, which are multi-billion dollar franchises with approvals only.
Speaker 4: and hormone receptor positive, hair two negative breaths, pants up.
Speaker 4: Two of them require a one-week drug holiday.
Speaker 4: And every fourth week
Speaker 4: mainly due to their bone maltoxicity.
Speaker 4: leading to neutropenia or a low white blood cell count.
Speaker 4: while the third requires twice daily dosing due to its shorter half-life.
Speaker 4: By dosing the rasa cycle once daily continuously,
Speaker 4: We can provide patients
Speaker 4: with a more convenient and safer dosing regimen from a marrow suppression perspective. They will not include a one-week-off drug holiday, during which tumor cells could potentially proliferate.
Speaker 4: in the absence of kinase inhibition.
Speaker 4: of their overexpressed pathways.
Speaker 4: Turning next to our investigator-sponsored rego-serta programs, our recent progress here was highlighted by Phase II data reported last month in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa.
Speaker 4: or R-DEB associated squamous cell carcinoma, for short.
Speaker 4: I'll let Mark detail this early data.
Speaker 4: But we'll note that given the results,
Speaker 4: the magnitude of the unmet need in our dev associated square micelle and its ultra-awful nature.
Speaker 4: We plan to seek guidance.
Speaker 4: from the FDA on the most expeditious path.
Speaker 4: boards a potential approval for Regal Assertive in this indication.
Speaker 4: In addition to highlighting
Speaker 4: these clinical accomplishments.
Speaker 4: Mark will preview upcoming posters on the razocyclic, our lead compound that will be presented at the AACR meeting.
Speaker 4: Orlando next month.
Speaker 4: We will also recap preclinical data on regal surgery that were presented at the recent AACR Targeting RAS conference.
Speaker 4: last week.
Speaker 4: Before I hand the call off to Bach, I'd like to highlight the important and recent appointments of Drs. Peter Vitaggia and Trafford Clark, who are board of directors.
Speaker 4: Together, Peter and Trafford bring more than 50 years of experience in the pharmaceutical industry to our board.
Speaker 4: having had key positions with increasing responsibilities at both Novartis and Eli Lilly respectively.
Speaker 4: in the short time since their appointments
Speaker 4: They've already provided invaluable insights.
Speaker 4: informed by their extensive knowledge of drug development leading to commercialization.
Speaker 4: Looking forward, I am eager to continue benefiting from their wise counsel.
Speaker 4: as we pursue our mission of discovering, developing, and delivering best-in-class products to patients with cancer. With that, I'll now turn the call over to Dr. Mark Gelder to provide more details and context. Dr. Gelder, thank you for joining us today.
Speaker 4: on our recent clinical.
Speaker 4: and scientific accomplishments. Mark.
Speaker 6: Thanks Steve!
Speaker 7: I'll start with a quick update on the rasocyclib phase 1 solid tumor program
Speaker 7: I'm going to focus on the program's US study referred to as Study 1901.
Speaker 7: This study is evaluating the continuous, once daily,
Speaker 7: awaiting the continuous, once daily dosing.
Speaker 7: that we plan to utilize with the Radocycline moving forward.
Speaker 7: The trial recently completed the fifth dose cohort.
Speaker 7: This was a cohort.
Speaker 7: of patients who took 200 milligrams a day.
Speaker 7: patients who took 200 milligrams a day by mouth.
Speaker 7: on a continuous daily basis, days 1 through 28, each cycle being 28 days.
Speaker 7: We expect it will advance to the sixth dose escalation cohort, which will evaluate the safety, tolerability, PK, and PD of a 240 mg dose of nirazacyclib.
Speaker 7: orally once daily.
Speaker 7: We expect to move to the sixth dose escalation cohort after the safety monitoring committee has reviewed the data from the fifth dose cohort. Data from the trial continues to be highly encouraging.
Speaker 7: with anticipated on-target effects of nirazocycline observed but in the absence of
Speaker 7: of any clinically meaningful cases of neutropenia or diarrhea.
Speaker 7: meaningful cases of neutropenia or diarrhea. This is important.
Speaker 7: Since as Steve pointed out, neutropenia is the dose limiting toxicity
Speaker 7: for two out of the three approved CDK4-6 inhibitors, while diarrhea,
Speaker 7: is the primary dose-limiting toxicity for the third one of Benacyclic.
Speaker 7: These early clinical findings are also notably consistent.
Speaker 7: with Narazasicin's differentiated kinase inhibitory profile, as well as its preclinical data that showed reduced neutropenia when directly compared to the most widely prescribed CDK46 inhibitor, palvocycline. On our last earnings call,
Speaker 7: You heard Steve and I speak about how Narasicilips differentiated inhibitory profile positions it as a potentially best in class therapy when combined with Lectrozole in patients with recurrent or metastatic low grade endometrial endometrial cancer.
don't count.
We expect the study to be open for enrollment.
later this quarter as planned.
and are very pleased that it remains on track for a preliminary data readout in the fourth quarter of this year.
very pleased that it remains on track for a preliminary data readout in the fourth quarter of this year. Several other sites. You'll find new research Bossman Eaton.
are on track to be open and up and running in the coming weeks.
track to be open and up and running in the coming weeks. As a reminder,
The scientific rationale for the neurosicyclic LGEEC
comes from a randomized placebo-controlled phase two study.
as well as a couple of different single arm clinical trials of the currently available CDK46 inhibitors, albocycline, ribocycline, and abemacycline in patients with estrogen receptor-positive endometrial cancer. For more information, visit CDK46.com
These trials all demonstrated the improved anti-cancer activity of CDK46 inhibitors when combined with Lectrazol when compared with Lectrazol plus placebo in the low-grade endometrioid endometrial carcinoma patient.
It was these trials that support the compendia listing of the three currently available CDK46 inhibitors that enabled their off-label use and reimbursement in this setting today.
However, I think it's important to realize that none of the currently available CDK46 cancers are FDA approved for the treatment of low-grade endometrioid endometrial cancer.
and they are limited by the shortcomings related to safety, powerability, and treatment resistance as we discussed before.
Given Naraziscyclin's ability to inhibit CDK4 and 6 with similar potency to palmosyclin, ribocyclin, and amamocyclin, we believe our phase 1, 2 trial has a high likelihood of technical and regulatory success.
Moreover, we believe our preclinical and Phase 1 findings.
suggests that nirazacycline may offer significant safety advantages compared to currently available agents.
And
Its ability to target additional proteins related to anti-tumor immunity, metastases, cancer cell survival, et cetera, may lead to improved efficacy. We therefore believe that naracacyclid has the potential.
to substantially improve the treatment paradigm for patients with recurrent, low-grade endometrioid endometrial cancer.
and look forward to evaluating this hypothesis in our Phase I-IIa trial.
Looking beyond low-grade endometrioid endometrial cancer, we are planning to initiate a clinical program of nirazocycline in one or more additional indications by the end of this year. And while we can't provide too much detail on these plans, we are planning to initiate a clinical program of nirazocycline in one or more additional indications by the end of this year.
clinical trials are currently being prepared for review, and we have identified key opinion leaders to serve as the principal investigators of the additional studies being planned.
To conclude my section on neuro-acid cycling, I want to briefly preview two posters on preclinical data that will be presented at the upcoming American Association of Cancer Research, or a Sullivan Center for AACR meeting.
next month in Orlando.
The first of these posters will feature results that demonstrate neurosiscyclic single agent activity against mantle cell lymphoma in vitro and in a chicken embryo chorioelectronic membrane xenograft model. The next poster will feature results that demonstrate neurosiscyclic single agent activity
And importantly, neurosopcyclops activity against mantle cell lymphoma cell lines
was found to be superior to that of pulvocyclic and ribocyclic and similar to that of Abemacyclic.
Moreover,
when the rasocycline was combined with ibrutinib.
A BCK inhibitor approved for the treatment of mal-cell lymphoma.
Synergistic increases in anti-tumor activity against both BTK inhibitor resistance and BTK inhibitor sensitive cell lines were observed.
The second poster that will be presented at AACR next month will compare the differential cellular targets that are engaged by nirazocyclib compared to the FDA approved CDK46 inhibitors.
In addition, results from a cell-based mammary cell carcinoma model show that
stronger induction of apoptosis with neurosiscyclin would deserve compared to pomel cycle.
as will data that will show neurosocyclic combining with autophagy inhibitors to sensitize breast cancer cells to cell death.
While the conference embargo policy prevents me from saying much more about the data featured in these two posters at this time, we look forward to having further discussions with the scientific and clinical community at the AACR meeting next month. Shifting gears.
I'll now discuss our investigator-sponsored Regal CERTa programs with a focus on the exciting early clinical data in the R-DEB-associated squamous cell carcinoma, which was reported back in February . In this video, I'll discuss the results of the R-DEB-associated squamous cell carcinoma
As those familiar with Acunova may recall, RDEB is caused by insufficient Type VII collagen protein expression. RDEB enter the
This deficiency in type 7 collagen leads to extreme skin fragility, chronic blistering, wound formation in these ardent patients.
many of whom go on to develop quite a cell carcinoma, frequently metastatic, that are driven by overexpression of PLK1.
of whom go on to develop squamous cell carcinomas, frequently metastatic, that are driven by overexpression of PLK1. Unfortunately,
All of the currently available treatments.
including targeted therapy, immunotherapy, conventional chemo therapy, radiation therapy, et cetera.
including targeted therapy, immunotherapy, conventional chemo therapy, radiation therapy, et cetera, provide only limited benefits.
or R-DEB associated squamous cell carcinoma patients.
who have a cumulative risk of death of 70% by age 45.
To address the unmet needs of patients with R-DEB-associated squamous cell carcinoma, we are working with multiple investigators on a Phase 2 program evaluating the safety and efficacy of regal serative model therapy in this patient population.
Last month, we announced that the trial second a valuable participant.
achieved a complete clinical response of all...
or skin lesions after only four cycles of therapy.
This patient remains on study.
with additional scans scheduled to monitor metastatic disease.
The announcement of the second patient.
follow data that showed a complete clinical response.
in the program's first evaluable participant, who has remained in complete remission with no signs of metastatic disease for more than 24 months.
while remaining on regal circuit. The studies remain open and are continuing to enroll patients.
and we are actively looking for additional sites to participate in the program.
While data from an NSF-2 must always be taken with caution.
The results from Regocertib's R-DEB-associated squamous cell carcinoma program have far exceeded our expectations as well as those of the trials investigated.
They have confirmed regal certain activity against PLK-1 in the clinic, as well as its ability to drive durable clinical responses in patients who have failed prior therapy.
As Steve mentioned, the next step for the program is now to engage with the FDA to align on the optimal regulatory path for the program given our data today and the lack of effective treatments that are currently available.
for patients with R-DEB associated squamous cell carcinoma. In addition, R-DEB is a catastrophic pediatric illness.
and this reality, as well as the potential enrollment of pediatric patients.
in the clinical program will be some of the topics to be discussed with the FDA.
Taking a broader view, we believe the results from Regal Serotonin's RWA-associated squamous self-personnel program may have positive read-through into other, more prevalent cancers.
characterized by PLK1 overexpression. This is a hypothesis being explored in preclinical studies, though I should note that any effort to advance research of clinical development and additional indications and personnel involvement over these past 10 years isballingly small, but doesn't kill people with cancer at the same time.
would be enabled by investigator-sponsored trials so that we can continue to dedicate our primary focus and resources on nirazocycline. Lastly, I'd like to touch on the status of the two investigator-sponsored trials evaluating Ricoh circuit in combination with a PV1.
in Philadelphia, Pennsylvania.
This data showed how Ricoh-Sertum...
and stimulate an anti-cancer immune response via activation of the NLRP3 inflammasome. Collectively, these preclinical data provide a strong mechanistic rationale for the aforementioned trials, which aim to leverage the
regrocerative immunotherapeutic effects to overcome checkpoint inhibitor resistance.
The first of these trials I'll mention is designed to evaluate Ricoceratid plus Pembrolizumab
in checkpoint inhibitor refractory metastatic melanoma.
I am pleased to say that this trial has recently been posted on clinicaltrials.gov, now has an NCT number, 05764395, and should be open for patient approval at Vanderbilt University Medical Center, Washington, D.C. For more information, visit www.cctexas.gov
later this quarter. We look forward to providing additional updates as this trial progresses.
The second rego-serative checkpoint inhibitor combination study I'll mention is the Phase 1, 2A trial evaluating rego-serative plus nivolumab in KRAS mutated non-small cell lung cancer patients. The next rego-serative checkpoint inhibitor combination study I'll mention is the Phase
who have failed prior therapy with a checkpoint inhibitor. We remain on track to report additional data from this trial in the first half of this year. This announcement will likely include updated data from the two patients who have failed prior to the accident.
to remain on study as of its readout at ESMO last year, as well as data from additional patients who were not yet enrolled and are valuable for efficacy as of the ESMO data had obtained.
After seeing these data, we plan to discuss them with the study investigator.
to determine the optimal next steps for this program.
And now with that, I'll pass the call off to Mark Garrett.
Thank you, Mark.
Onkinova finished 2022 in a strong financial position with cash and cash equivalents of $38.8 million as of the end of the year.
This compares with cash in equivalence of $55.1 million at the end of 2021. Based on our current projections, we believe our current cash position will be sufficient to fund our ongoing clinical trials and operations into the first quarter of 2024.
This cash runway is expected to take us through key milestones, including a first data readout from our combination trial of neurotic glyclic and lethresol in advanced endometrial cancer later in 2023. Turning now to our full year financial results, research and development expenses for 2022 were $11.4 million.
compared to $7.3 million for 2021.
General and administrative expenses for 2022 were $8.4 million compared to $9.4 million for 2021.
Our net loss for 2022 was $19 million or $0.91 per share on 20.9 million weighted average shares outstanding.
This compares with the net loss for 2021 of $16.2 million, or 96 cents per share, on 16.8 million weighted shares outstanding.
The increase in net loss for 2022 compared with 2021 was primarily a result of higher spending in the Naraza Cyclist Development Program and drug manufacturing in 2022.
That completes my financial review. I'll now pass the call back to Steve. Thanks to both of you box.
I'll start my closing remarks by thanking all of those.
who made the progress we spoke about today possible.
made the progress we spoke about today possible. At the top of this list,
our clinical trial participants
our clinical trial participants and their caregivers.
whose bravery is a constant source of inspiration to all of us. I'd like to also thank our employees, investigators, partners, and shareholders for their support.
which has us advancing towards multiple key milestones that you heard about today.
they are expected between now and the year end. In our neuropsychic program, we expect to report preliminary data.
from our combination trial of neurosiscyclobenetrazole and advanced endometrial cancer in the fourth quarter of this year.
We also expect continued progress about Phase I trials to enable the selection of a recommended Phase II dose in the first half of the year.
and to initiate a clinical program of niragicyclib in one or more additional cancer indications.
Regarding legal assertive, we look forward to discussing our recent R-DEB-associated squamous cell carcinoma data.
Regarding legal assertive, we look forward to discussing our recent R-DEB associated squamous L-carcinoma data with the FDA.
in order to help determine the optimal regulatory pathway of these exciting clinical outcomes. We also look forward to opening the combination trial of Vigocerta and Pimuluzumab in melanoma later this quarter.
and expect that the phase 1, 2-way trial of rigor serota plus nivolumab in the KRAS mutated non-small cell lung cancer will have additional important data.
2-way trial of rigor serota plus nivolumab in a KRAS mutated non-small cell lung cancer will have additional important data to report.
in quarter two. In parallel with the progress of our clinical programs.
We will continue to evaluate potential opportunities to expand our pipeline,
and will focus any such efforts on assets that have a strong body of evidence.
demonstrating their best in class potential in an indication with a high unmet medical need.
We plan to be very highly selective as we make this corporate
development assessment as our current programs are backed by compelling data.
and provide us with multiple shots on goals.
provide us with multiple shots on goals and opportunities.
to generate value for our investors and the patients.
With that, we'll begin today's Q&A session.
I got worried. Ladies and gentlemen, if you wish to register for a question for today's question and answer session, you'll need to press star then the number one on your telephone. Thank you.
If your question has been answered or you wish to withdraw your request, you may do so by pressing star 1 again. If you're using a speakerphone, please pick up your handset before entering your request. One moment please for the first question. And our first question comes from Charles Zhu from Guggenheim Securities. Please go ahead. Your line is open. Your line is open.
Hi guys, this is Edward on for Charles Zuba at Guggenheim. My first question is on a NARS-O-Pi-Clib, the Monotherapy Dose Escalation. I'm curious if you can give any more color on how the Dose Escalation is going beyond the prepared remarks. Do you think you're in the potentially therapeutic, therapeutically efficacious range for the doses and how much higher do you think you could go?
And then as a potential and as a follow up, I know you've guided to the Electrozole combo data in 4Q, but so how should we be thinking about the the monotherapy, just escalation data update? Could that come before the 4Q update?
Thanks, Ed. I'll ask Dr. Geltz to take that, please. Sure. So.
What I can tell you is that we do believe that we're getting close to a PC
quote unquote, dose that we can use as our recommended phase 2 dose. We are beginning to see some effects that we would anticipate from a CDK46, i.e., we're beginning to see a little more grade 1.
grade 2 neutropenia. We're not seeing a whole lot other than that. We're seeing some low-grade diarrhea, but nothing significant. The PD work, the pharmacodynamic work with the 200-milligram cohort is still pending. It's still out. So I can't say anything for certain about that.
But just based on what I'm seeing, do I think that we're getting relatively close? Yeah, I do. Does that mean 240 milligrams is going to be the dose? 280 milligrams.
You know 320 milligrams. I don't know do I think we're gonna have to push this to five or six hundred milligrams No, I do not so I I do think we're getting closer But I can't give you a firm answer today. Yeah
And Mark II questioned what the strategy of the monotherapy trial when we also already begun the combo trial with letters of...
And Mark, the second question was the strategy of the monotherapy trial when we also have already begun the combo trial with Letrozole. Make some comments on that.
You know we're looking at
different options right now. You know, whether we do continued work with, in combination with either Lectrozole or other anti-estrogens.
whether we do work
as a monotherapy, whether we do some continued work with the rasocycloib in combination with say a checkpoint inhibitor or in combination with a BTK inhibitor or in combination with a MEK inhibitor, we're looking at several different options now. So I can't.
give you any more specific details at this time. What I will tell you is that we do have, we believe we do have several good options in terms of additional development programs to start moving forward with other than.
the low-grade endometrioid endometrial cancer. And so exactly what our second program and third program and fourth program will look like at this time, I just can't say. Steve, you may want to give a little more away, but I'll hold my comments there.
I think I think Ed's question and correct me if I'm wrong Ed is how do how do we start a combination trial with neuropsychic before we know the recommended phase two model therapy dose. So I think the answer Ed.
The answer is that as a Dr. Gell to said we believe we're close.
the recommended phase two dose. And anytime you do a...
Phase 1 new combination, you always
decrease the dose of the experimental agent, in this case, an accident can arise with cyclists.
So since we think we're close, we went back one step, one cohort, picked that dose of nirazosiclip in combination with etrozole, and in a three by three design, we'll again continue to increase the dose of nirazosiclip in combination with etrozole, based on the formula we had before.
The safety profile that Dr. Geldo will be observing. So I hope that answers your question.
That's great. Thank you. All right. Thank you.
That's great. Thank you. Thank you.
Our next question comes from Ahu Damir from Ladenburg-Dalman. Please go ahead, your line is open. Good evening. Hello team. Thanks for taking my questions and congrats on the progress. I have two questions. One of them, we heard you say the entity was not rich and also you don't observe the Neutrosynea and diarrhea.
I am curious to hear if you could provide more color on the similarities or differences between nares of cyclic with other CDK4-6 inhibitors. Do you observe similar safety profile or is it very differentiating? If you could provide some color on that, that would be helpful. I am curious to hear if you could provide some color on that. Do you observe similar safety profile or differences between nares of cyclic with other CDK4-6 inhibitors?
to hear if you could provide more color on the similarities or differences between nares of cyclic with other CDK4-6 inhibitors. Do you observe similar safety profile or is it very differentiating? If you could provide some color on that, that would be helpful. Thank you.
Yeah, so I think when I look at what really differentiates us, you know, as you're well aware, Algo and Ribo are the two, quote unquote, purists.
CDK46 inhibitors with Ribo being the purest followed closely by Palba.
Abemacyclib, like nirazacyclib, is truly a multi-targeted kinase inhibitor. It hits several different kinases at low nanomolar concentration.
But the kinases that Abemacyclib hits are very different than the kinases that Norazacyclib hits. All of them are very potent, very effective CDK46 inhibitors. What differentiates Norazacyclib are the other kinases that are not as potent as the other kinases that are not as effective CDK46 inhibitors.
that it hits at low nanomolar concentration, particularly the Arc5 or NUAC1 and the CSF1R. But there are others.
the FLET3, the C-KIT, et cetera. So there are actually several kinases that we hit that we think have the potential to address the potential.
to be very important in terms of the overall efficacy.
as well as the safety of neurasyclic.
This is all preclinical data. We're just getting into the clinic. We've now had in our phase one dose escalation study, we've now had 21 patients total who have been exposed to the Neurozasticlin at escalating doses. And as I said so far, the safety profile looks very, very good.
very similar to what we had anticipated based on all of our pre-plenical data. And we are very excited, as we've said, to be moving into the low grade endometriode and the metrol cancer study because now, rather than using a...
a typical phase one solid tumor population, we will be using a population where we expect, where we anticipate to start to see some really significant activity. So this is sort of where we are. I hope that answers your question.
But it all has to do with the other kinases that we had. And actually, I heard there will be more data that...
As Mark alluded to, there will be greater detail at the AACR meeting in Orlando. That's helpful. Thank you. I have one more question on the lateral bone combination trial. For the...
drugs are administered daily. I am curious if you have looked at the safety profiles, are there any overlapping toxicities? Are you expecting anything major in the combination trials? So when I look at Lekkerzol and it's
it's got a very well established AE profile. And when I look at what we've seen so far with nirazocycline and what we expected based on the other CDK46 inhibitors that are already approved and based on our preclinical data.
there really is very little, very little, overlapping toxicity of the two. The biggest one is really fatigue.
And if I can add.
to that and also add to the previous question. Of course, that is all of the anti-Sugin and as Mark just said, a very different
safety profile and a very acceptable safety profile, a very different mechanism of action.
as an anti-estrogen. That's why rather than waiting to re-wait.
for the recommended phase two dose of mono-neurazosyclin study to read out, we are comfortable combining the neurazosyclin with let's resolve with a lower dose of neurazosyclin to make sure we stay safe.
But this approach of already opening.
The combination trial in endometrial saves us two key factors.
which are both very important, time and money. So we now will have, as we mentioned in this quarter, the first patient on this combination trial with endometrial cancer. Dr. Peter Sal bias and Think line 10 and rehearsals domestic issue
both very important, time and money. So we now will have, as we mentioned in this quarter, the first patient on this combination trial with endometrial cancer, studying the combination.
Thank you. Thanks for taking my questions. Our next question comes from Jo Janis from HC Wainwright. Please go ahead. Your line is open. Your line is open.
Hey guys, good afternoon. Thanks for taking the question. So this might be jumping the gun a bit here. Obviously, you need to talk to the FDA first with regard to rigosuratib potential in the RDEV. But with that said, do you have, I guess, any sort of broad strokes to take right now, both internally and internally?
and maybe from any external sort of regulatory consultants that might give you an early wishlist that you can share with us regarding a potential design. Well, the wishlist, Joe, won't require a design.
The results that Dr. Gelder shared with us, the patients and the experts who see these patients are extraordinary. They have failed everything else.
And as we mentioned, we have complete cutaneous responses. This is an ultra rare disease.
and we have already demonstrated complete responses and nothing else works. Our regulatory consultants are the ones saying we should go to the FDA now and ask the question, what will it take?
to get regrocerative approved in SqMSL complicating our DEB. We don't know if the current two patients are enough. Will they want an additional two patients? We really don't know what the end is going to be. And as Mark said, hopefully before we meet with the FDA, maybe we'll have one or two additional patients. The incidents that are usually described
of this disease in the U.S. is about 100 odd dead patients a year, maybe 50 live long enough to develop squamous cell carcinoma, but it's very hard to identify these patients, as you know. In addition, the other wish is, because this is a pediatric disease, it's easy on them.
expresses itself in the pediatric age population. We are told that periodically a child is seen with squamous cell, mostly the young adults who develop the squamous cells. The two patients that we treated are, in fact, young adults. This will be presented in greater detail at the International...
out there anywhere in the globe that we become aware of, we of course would be very interested in treating that child with rego-certum and discussing the possibility of a pediatric voucher for squamous cell complicating our death. So those are our wish lists to get rego-certum approved with this indication.
I can discuss the possibility of a pediatric voucher with the FDA.
the possibility of a pediatric voucher with the FDA. Very helpful, Steve. Thanks a lot.
Our next question comes from Robert LaBoyer from Noble Capital Markets. Please go ahead, your line is open. Good afternoon. I had a question that I think was partially answered earlier but if you're going into a sixth cohort for neurons a cyclic
Could you?
Give it any kind of time frames as to when the six might be completed or the seventh or even an eighth if you go that far and When you might start the phase two
Mark? So it's impossible to say when a cohort is going to get completed. You have a 3 plus 3 design, and it depends on if you get a DLT. It depends on how many screen players you have, et cetera, et cetera. So, if you have a 3 plus 3 design,
Typically, it takes, if you don't have any significant problems, don't have a lot of screen failures, et cetera, you can complete a cohort of three in two to three months. If you have a DLT and then have to expand it out to six or...
if you start having several screen failures, et cetera, it can take four, five, six months to complete a single cohort. So it's really impossible to say. Our fifth cohort, as you're all well aware, took several months to complete because we had several screen failures, et cetera.
but that's just the nature of clinical research. The first four cohorts, we all completed. We completed each one of them.
nature of clinical research. The first four cohorts we all completed, we completed each one of them in two to three months.
And in terms of how many cohorts we're going to have to go, I do not have a crystal ball. I can't tell you. Do I, in my gut, do I think we're probably getting close? Yeah, I do.
The sixth cohort is at 240 milligrams. Will that be as high as we need to go, or do we need to go to 280? That decision won't just be driven by the AE profile. It will also be driven by the PD data, the pharmacodynamic data, because we're going to...
look for a dose that maybe isn't the MTD or maximal tolerated dose, but look for a dose where we see you know maximal biological effectiveness too. So it's just hard to say.
Okay, thank you very much.
Okay, thank you very much.
I'm showing no further questions in queue. At this time, I'd like to turn the call back over to the speakers for closing remarks. Thank you all again for joining today to hear about our recent progress.
outlook for the rest of the year. We're obviously excited to be nearing several important clinical milestones.
and appreciate your continued interest in the important, if not crucial work we are doing.
Thanks again and enjoy your evening. I look forward to seeing many of you going forward. Thank you. Ladies and gentlemen, thank you for your participation on today's conference call. This concludes today's event. You may now disconnect.
I have.
The I.
Thanks for watching!
You.