Q4 2022 Cyclacel Pharmaceuticals Inc Earnings Call
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Speaker 2: Good afternoon and welcome to the CycloCell Pharmaceuticals fourth quarter and full year 2022 results conference call on Webcast.
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Speaker 2: I would now like to turn the call over to the company.
Speaker 3: Good afternoon, everyone, and thank you for joining today's conference call to discuss Cyclosel's financial results and business highlights for the fourth quarter and full year of 2022. Before turning the call over to management, I would like to remind everyone that during this conference call, the
Speaker 3: Forward-looking statements made by management are intended to fall within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and Section 21e of the Securities Exchange Act of 1934 as amended.
Speaker 3: Asset for us in our press release, forward-looking statements involve risks and uncertainties that may affect the company's business and prospects, including those discussed in our filings with the FTC, which include, among other things, our Form 10K.
Speaker 3: This filing is available from the SEC or our website. All of our projections and other forward-looking statements represent our judgment as of today and Cyclosel does not take any responsibility to update such information.
Speaker 3: With us today are Spiro Rombadis, President and Chief Executive Officer.
Speaker 3: Paul McBarran, Executive Vice President, Finance, and Chief Operating Officer, and Dr. Mark Kirschbaum, Senior Vice President and Chief Medical Officer.
Speaker 3: The Bureau will begin with an overview of our business strategy in progress. Mark will provide details on Psychosell's clinical programs, and Paul will provide financial highlights for the fourth quarter and full year of 2022, which will be followed by a Q&A session. Bring your E badly loved ones with you, it probably won't seem like they'll see you
Speaker 3: At this time, I would like to turn the call over to Sphero.
Speaker 4: Thank you, Irena, and thank you everyone for joining us today for our quarterly business update.
Speaker 4: In 2022, we made excellent progress.
Speaker 4: in our ongoing Phase 1-2 clinical programs with oral fadrocyclide or FADRA.
Speaker 4: and oral plogostertib or Plogo in patients with solid tumors and lymphoma.
Speaker 4: Both programs are registration directed
Speaker 4: and are well positioned to deliver on key milestones.
Speaker 4: during 2023. In the FADRA study in patients with solid tumors and lymphoma,
Speaker 4: We have enrolled three patients at dose level 6A.
Speaker 4: Recent pharmacokinetic and pharmacodynamic data from this dose level suggest that we are achieving target engagement levels on continuous dosing, which are commensurate or better than those observed in dose level 5 patients.
Speaker 4: We will enroll three more patients at those level 6A, Proportical, with the objective of determining that a commended phase two dose or RP2D.
Speaker 4: At our R&D day in October 2022, we reviewed clinical activity observed in the first five dose levels of the study.
Speaker 4: We were excited to see monotherapy partial responses, or PRs, after the first treatment cycle in lymphoma patients with both cutaneous T-cell lymphoma, or CTCL, and peripheral T-cell lymphoma, or PTCL. This included a PR with a difficult to treat type of PTCL.
Speaker 4: In addition, 11 patients with various solid tumors achieve stable disease with target lesion reductions.
Speaker 4: and a pancreatic patient maintains stable disease for five cycles of treatment.
Speaker 4: As we approach the completion of the Phase I Dose Escalation Stage of the FADRA Study,
Speaker 4: We look forward to starting the Phase II Proof of Concept, or POC, stage.
Speaker 4: This will consist of multiple cohorts defined by histology.
Speaker 4: which are designed to be recruited in parallel, thus avoiding the delays inherent in sequentially designed studies.
Speaker 4: We expect that cohorts may enroll at different rates.
Speaker 4: It is possible that the fastest ones will be those in which we have already seen anti-cancer activity during the total escalation stage.
Speaker 4: Clinical data from this open label POC stage will be reported as they become available.
Speaker 4: At the R&D day, we also reported exciting new findings from our Plogo program.
Speaker 4: which focuses on PLK1 inhibition
Speaker 4: for the treatment of advanced solid tumors and lymphoma.
Speaker 4: Plogol has already shown early signals of anti-cancer activity at the first dose level in patients with non-small cell lung and ovarian cancer.
Speaker 4: We also have evidence demonstrating Plogo's differentiated biological profile.
Speaker 4: Dose escalation in the PLOGO study has advanced and sites are currently submitting patients for dose level four.
Speaker 4: Over the course of this year, we expect key data readouts from the Phase I-II studies for FADRA and PLOGO.
Speaker 4: We expect to report complete dose escalation data with FADRA around the middle of the year.
Speaker 4: Initial data from the FADRA Phase II B or C stage are expected in the second half of 2023.
Speaker 4: Dose escalation in the PLOGO study continues, and we expect initial data in mid to late 2023.
Speaker 4: Before handing over to Mark, I would like to reiterate that the cyclosol team is concentrating our efforts on bringing our two molecules to proof of concept stage in creating shareholder value.
Speaker 4: We are well on our way to achieving that with FADRA.
Speaker 4: and we will soon be in a position to potentially do the same for POGO.
Speaker 4: We are fortunate to be working with world-class institutions across the globe who are participating in our studies.
Speaker 4: We believe that our medicines are differentiated from other molecules in their respective class with properties which may be best in class.
Speaker 4: I will now turn the call over to Dr. Mark Kirschbaum, our Chief Medical Officer, to provide details on recent clinical data. Mark?
Speaker 4: We'll now turn the call over to Dr. Mark Kirschbaum, our chief medical officer, to provide details on recent clinical data. Mark? Thank you, Stirl.
Speaker 5: We are pleased with the single-agent activity and molecular profile of oral FODRA and the encouraging progress of oral Plogo in our phase one studies.
Speaker 5: Once the recommended phase 2 dose is determined in the ongoing 065-101 study with oral Foudra, we will immediately move into phase 2 proof of concept stage in which the primary objective is to assess activity and safety of the drug in relevant tumor types. At ENA 2022, the
Speaker 5: an hour R&D day in October , we reported on the dose escalation part of the study.
Speaker 5: FODRA was well tolerated and escalated from dose levels 1 to 5, which is 100 mg twice daily Monday through Friday for 4 weeks out of 4.
Speaker 5: Dose level 5 is completed and can be considered safe. There have been no dose limiting toxicities related to study drug.
Speaker 5: In dose levels up to five, the only consistent side effect of the drug is nausea at manageable levels, typically grades one to two.
Speaker 5: As per protocol, we escalated to dose level 6, which is 150 milligrams twice daily, Monday through Friday, for four weeks out of four.
Speaker 5: At that dose level, we observed two grade three dose limiting toxicities at dose level six.
Speaker 5: hyperglycemia in one patient, and nausea in a second patient.
Speaker 5: Both were reversible after holding drug. In accordance with the protocol, we have enrolled three of a plan six patients at dose level 6A, which is 125 milligrams twice daily, Monday through Friday, for four weeks out of four. At this stage of the study, we seek to optimize the dose and schedule and then commence the phase two stage.
Speaker 5: As reported, we have seen anticancer activity in the dose escalation up to level 5.
Speaker 5: Two out of three patients with T cell lymphoma achieved PR, including a patient with a very aggressive angioimmunoblastic form of peripheral T cell lymphoma.
Speaker 5: Eleven of 15 patients with cervical, endometrial, liver, and ovarian cancers achieved stable disease with target lesion reductions as their best response.
Speaker 5: A pancreatic patient maintains stable disease for five cycles of treatment.
Speaker 5: These are promising responses for this earlier phase of clinical testing and may predict deeper responses in the phase 2 stage.
Speaker 5: With regard to our second oral FODRA study, 065102, in patients with acute myeloid leukemia and myelodysplastic syndromes, we are enrolling patients at dose level 5, which is 100 milligrams twice daily, Monday through Friday, for four weeks out of four.
Speaker 5: We look forward to providing an update on the 065102 trial during the year. Let's now turn to our second program with Togasertib, our oral PLK1 inhibitor.
We have reported initial encouraging results from 140.101, our phase 1-2 study of PLOGO in patients with advanced solid tumors and lymphoma.
This study is currently enrolling at dose level 4, which is 15 milligrams once a day, Monday through Friday, for weeks 1 and 3.
This is a first in human study for oral PLOGO and, as is traditional, we have started at lower doses. We were therefore pleasantly surprised at this early stage of the study to observe stable disease at dose level one in two patients with non-small cell lung cancer for eight cycles and ovarian cancer for five cycles, respectively.
and at dose level 2 in a patient with biliary tract cancer for three cycles. Published preclinical evidence suggests that low-dose continuous administration may be an effective strategy for PLK1 inhibitors, as well as the more documented higher-dose pulse type strategy.
This is particularly true for PLOGO, given that it has a favorable PLK inhibitory profile and a shorter half-life, thus potentially minimizing toxicity.
Our ongoing Phase 1-2 trial of FLOGO is designed to target several important tumor types, where the drug may show broad single agent activity.
This was observed across multiple preclinical models and in particular colon cancer, lymphoma, and small cell lung cancer.
Our study efficiently evaluates both dose and schedule so as to optimize the recommended phase two dose for the proof of concept or cohort stage of the study.
I will now turn the call over to Paul to review our fourth quarter and full year financial results.
call over to Paul to review our first quarter and full year financial results. Thank you, Mark.
As of December 31st, 2022, cash and cash equivalence totaled $18.3 million compared to $36.6 million as of December 31st, 2021.
Net cash used in operating activities was 20.8 million for the 12 months ended December 31st 2022, compared to 18.5 million for the same period of 2021.
On a pro forma basis, cash and cash equivalents totaled $23 million, which includes $4.7 million of R&D tax credits receivable in the second quarter of 2023.
The company estimates that its available cash will fund currently planned programs into the fourth quarter of 2023.
Research and development or R&D expenses were $6.7 million for the three months ended December 31st, 2022, as compared to $4.6 million for the same period in 2021.
R&D expenses related to FADRA were $5.3 million for the three months ended December 31st 2022 as compared to $3.4 million for the same period in 2021 due to the increase in clinical trial costs of $3 million associated with ongoing clinical trials evaluating FADRA.
the Phase 1-2 study, an increase of 1.6 million in non-clinical expenditures. R&D expense related to PLOGO were 1.3 million for the three months ended December 31st 2022 as compared to 1.1
due to clinical trial costs associated with the PLOGO phase 1-2 study.
General and administrative expenses for the three months ended December 31st 2022 were 2.1 million, compared to 1.9 million for the same period of the previous year due to an increase in employment and professional costs.
Total other expense net for the three months ended December 31st 2022 was 0.2 million compared to an income of $43,000 for the same period of the previous year.
The decrease of 0.2 million for the three months ended December 31st 2022 is primarily related to foreign exchange adjustments.
The United Kingdom Research and Development Tax Credits were $1.6 million for the three months ended December 31, 2022, compared to $1.2 million for the same period of the previous year and are directly correlated to qualifying research and development expenditure.
Net loss for the three months ended December 31st 2022 with 7.4 million compared to 5.3 million for the same period in
Operator, we are now ready to take questions.
At this time if you would like to ask a question, please press star 1 on your telephone keypad.
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We'll take a question from Jonathan Ashoff of RothMKM. Your line is open.
Thank you guys. Hi, just a brief first question. Is that R&D rate kind of a minimum new quarterly rate, you know, such that the 4Q that'll be at least a level in each of the 2023 quarters?
Jonathan, thanks for the question. It will be for the first quarter but in the United Kingdom they are changing the tax rate so it will drop from the 4.7 probably down to about two a quarter going forward.
Do you say that R&D is only going to be two a quarter going forward? No, I thought you asked for the R&D tax credit. No, no, no, no. I'm asking for your GAAP reported R&D.
So the R&D will be consistent with the fourth quarter going forward into 2023, yes. Okay, thank you. The second question is what can you say about the indications in which FADRA and PLOGO are already looking the most effective? Well, this is Spiro. Thank you, Jonathan.
I think we can say that the lymphoma indication is the one that we feel the most encouraged, having seen early single-agent responses without toxicity in patients. Obviously, as we open the Phase 2, this indication, maybe together with women's cancers like endometrial and ovarian, are the ones that would likely enroll the fastest. And the reason, of course, is that we have a lot of patients who are not able to enroll
activity in B cell lymphoma, but they had enormous anxieties such as tumorizes syndrome that has not been reported for fadracycline in this studies. And also we expect some other women's cancers and possibly correctal and liver cancer might be of interest given early indication of activity.
So I think that lymphoma and women's cancers are the ones that we feel most comfortable. For Plogo, I think it's early days. We're obviously seeing prolonged stable disease in the very first dose level, which is almost at homeopathic levels, in lung and also ovarian biliary. But I just think that we need to wait for one or two more.
Asian approval goal as fast as you can.
Well, that is certainly our primary objective in the event that we continue to see single-agent activity. As we all know, the combination strategy, although producing substantial revenue opportunity, does take more time and more capital. The protocol as written for both FADRA and PLOGO allows for combination.
And the work is underway not only to prepare for that, but also to do the clinical work to assess combinability and safety of FADRA, for example, with other agents that are suitable depending on the tumor type. But it's fair to say, as you correctly pointed out, that our primary goal is to see if we can get a monotherapy indication developed.
up until POC and then approach regulators. Okay, and lastly, this is a quick one. What can you say about enrollment numbers between your last call and this call versus the second and third quarter call? I think this is a question for Mark.
Yeah, enrollment is going very quick in both studies.
we have we pretty much fill all the all the slots the day we open
So, yeah, we don't see any problem there.
Yeah, I mean, it seems to actually be fairly quick, whereas a lot of companies, on those things, kind of like there's still have this COVID hangover or something.
We didn't have any of that. Fortunately, we, uh, yeah, I think partly because we're oral and because the drug is very well tolerated. We definitely don't, certainly..
So, you know, the investigators have been very eager to put patients on.
Thank you very much.
Thank you, Jonathan. And once again to ask a question that is star 1 on your telephone keypad. We'll move next to Ahu Damir of Landenburg. Your line is open.
Good afternoon. Thank you so much for taking my question. My first question is, looking at the 101 and 102 studies of FADRA, do you see similar safety profiles in the patients, given the populations are very different?
Thank you for your question. This is a question for Mark. Yes, we haven't seen extraordinary problems in the leukemia study.
we actually have no SAEs reported there in the in FADRA. It's the in the solid tumor trial it is we've been clean on them all the way through to the current dose level so yeah I don't see any difference between the two.
My follow-up question is on the target engagement. Do you do any target engagement work and are we going to see any data from those?
Both for Fodrosychlip and Klogel. We are certainly doing targeting engagement work. This is central to our understanding of both drugs. Obviously Fodros more advanced and I would like Mark to speak specifically of what type of studies we are doing to confirm exposure of a threshold, which is critical for such agents.
but also is important for us as we build confidence about enrolling a successful phase two. I think many companies rush into phase two without fully understanding pharmacodynamic exposure as well as effect on pharmacodynamic markers and then try to sort of step back from phase two and see if they can crack the problem and that becomes a quagmire. We are gonna.
was done from the beat before the study started so we we have an established set of values for which we we know that cdk2 and cdk9 are inhibited by the drug which has been our benchmark against which we've been looking at our you know current PKs and PDs as we're moving forward
As far as PDs go, I think what we're trying to get at is that we're now, particularly in these dose levels that we're at now, we are certainly seeing the...
targets being hit that we anticipate and that we believe that this drug is a MYC inhibitor and MCL-1 inhibitor and we're seeing that activity in the PV samples that are drawn on the current patients that are involved.
Is that the answer to the question? Yes, it is. My last question is for Paul. Paul, on the SG&A side, are we expecting a similar trend moving forward in the subsequent quarters?
Yes we are. It will sit around the two to two point two million on a quarterly
Thank you very much for taking my questions. Thank you. Let me just add as a segue to Mark's comment that we're also seeing second E levels coming down, which is also an important target part of the CDK2 target profile of FADRA. So we're very pleased that we're seeing this level of confirmatory activity in patient samples. Thank you.
Our next question is from Jeff Jones of Oppenheimer. Good afternoon, guys, and thanks for taking the question. Two questions.
What do you need to see in the 6A arm to have comfort to move ahead into the proof of concept cohort? And over how many cycles do you need to see that?
And then on the financial side, how much cash is needed to complete the three ongoing clinical studies?
And how much additional are you thinking you need to do the proof of concept study for FADRA? Thank you. I think your first question, Jeff, is for Mark. Yes, please. I can take that quickly. That's a happy question. So we...
I mean, the good news is that we already know from the PD that we have on the patients in that sample that we're hitting the targets that we want to hit. So that looks good. 6A looks good to us. What we have to do now is just confirm the tolerability. So we need to complete this first.
dose level and that'll happen very soon. If that goes through then there we'll go to we'll go to six patients and and call it and call it the an acceptable dose. So that that's coming up soon.
And let me turn it back to Spero for the other questions. It's actually Paul's question. Yeah. So let me take that question. Thank you very much. So as we've mentioned, we have cash that runs through to the end of this year, Q4 2023. The way that we have budgeted that is to clearly run to tough
phase 2, up into the phase 2 for FODRA, the oral FODRA in the solar tumors and infirma. As once we get through RP2D, start the phase 2, we're budgeted to get into POC and we believe with our milestones that we'll be able to report out of the POC.
this current year within the current cash envelope. The other two studies were currently assuming we will get to dose escalation again within 2023.
Thank you. And once again that is Star 1 to ask a question. We'll move next to Bert Balliter of Brookline Capital Markets. Your line is open. Ben and Belle continuing
Hi, this is Kemp Oliver.
Hi, this is Kemp Oliver.
Quickly on the timing of readouts and the cadence, what's your sense as to how they will play out during the year?
Hello, Kemp. Thanks for your question. We think that obviously, the declaration of RP2D for FADRA, the 101 study in solid tumors and lymphoma is probably the most important milestone for the first half of the year. The company plans to make an announcement once we reach that critical milestone. And as you already are aware, we are going to be looking at the
The protocol is seamless, it moves straight into phase two. So we expect the next batch of milestones for that study will come from initial cohorts that will roll fastest. We mentioned in a previous question that we think that's likely to be lymphoma in women's cancers. And since this is a futility study, it's based on X responses over Y and release in that cohort, we expect to report.
that's, as Paul just mentioned, will probably get to the fluid dose escalation stage, to the proximity of Rp2D, but there may be some crosstalk between the leukemia study and the Soviet humor study. That often happens. And of course, we always be looking to finish the progositive phase one dose escalation component.
and hopefully get as close to our P2D as we can with the important qualification. But in that program, low dose may be sufficient to achieve target engagement and PD levels. So that remains to be determined of course, but that is a potential readout as well within 2023.
That's a very helpful thing. How are you thinking about the prioritization depending on, and again, we're in an environment where the incremental dollars have been harder to get and you may get all the capital you need quickly or it may be a challenge but...
Is it fair to assume that FADRA going into phase two, if you had to focus on one priority initially that's where you would direct the capital? Yes. Well, we live obviously in risk mitigation across all programs, but you are correct. In that situation, we just portrayed FADRA.
has been a field of great interest to pharma for many years. As many of the audience know, there have been a large number of programs in the next generation CDK family. Phybria is one of the leading, it was the leading program in this area, so it has obviously been on the radar of many companies. The second reason is the scarcity value of this drug.
I think that as we learned from Ash and earlier on other conferences of 2022, Fabry is so far the only drug in the next generation CDK family to have single agent activity and a good reliability profile. Especially if we think about the medical need and inform us.
in particular T-cell lymphoma and endometrial ovarian and other women's cancers. I think it's clear to see why Frost's remains by far the biggest value driver for the company in the year going forward.
Very helpful, thank you. Thank you, Kim. And it does appear that we have no further questions at this time. I'd be happy to return the call to our host for any concluding remarks.
Thank you, operator, and our thanks to all of you for joining the CycloCells fourth quarter and full year earnings call. The key takeaway from today's call is that as momentum builds with our two clinical programs, there is a potential of becoming important anti-cancer therapeutics.
in solid tumors and lymphoma is becoming apparent in both medical and industry circles. As a reminder, our key milestones for 2023 are report final data from dose escalation stage and recommended phase two dose determination from the 065-101 study of oral fibrosis.
Report interim Phase I data from 140.101 study of oral plogosertib in patients with advanced solvitumors and lymphoma. Report interim data from initial cohorts in Phase II proof of concept study of 065.101 to Nestor Item 4.
with oral phadrocyclib in patients with advanced solid tumors and lymphoma. Report interim data from dose escalation stage of O6-5-102 study with oral phadrocyclib in patients with advanced leukemia and report final data from dose escalation stage of 140-101 study with oral proboscity in advanced solid tumors and lymphoma. We look forward to providing you with further updates and hope to meet some of you at upcoming conferences.
Operator, at this time you may end the call. This does conclude today's conference. You may now disconnect your lines. And everyone, have a great day.
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