Cyclacel Pharmaceuticals Inc (CYCC) 2022 Q2 法說會逐字稿

And welcome to the Cyclacel Pharmaceuticals Second Quarter 2022 Results Conference Call and Webcast. (Operator Instructions) The company will also be accepting a limited number of questions submitted via e-mail to the address ir@cyclacel.com. (Operator Instructions) Please note today's call is being recorded.

I would now like to turn the conference over to the company.

Good afternoon, everyone, and thank you for joining today's conference call to discuss Cyclacel's financial results and business highlights for the second quarter of 2022. Before turning the call over to management, I would like to remind everyone that during this conference call, 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. As set forth 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 SEC, which include, among other things, our Form 10-Q. 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 Cyclacel does not take any responsibility to update such information.

With us today are Spiro Rombotis, President and Chief Executive Officer; Paul McBarron, Executive Vice President, Finance and Chief Operating Officer; and Dr. Mark Kirschbaum, Senior Vice President and Chief Medical Officer. Spiro will begin with an overview of our business strategy and progress. Mark will review Cyclacel's clinical programs, and Paul will provide financial highlights for the second quarter of 2022, which will be followed by a Q&A session.

At this time, I would like to turn the call over to Spiro.

Thank you, Irina, and thank you, everyone, for joining us today for our quarterly business update. The major highlight of the second quarter was our midyear update on June 30 at which we reported initial clinical results with oral fadraciclib or fadra for short. Fadra, our lead product candidate is an orally available CDK2 and CDK9 inhibitor enrolling patients in a Phase I/II study for the treatment of solid tumors and lymphomas, designated 065-101. Thus far, we have enrolled 17 patients in the dose escalation part of the study, reaching dose level 5 without dose limiting toxicities.

Based upon preliminary results in the first 5 dose levels with fadra dose daily, we are highly encouraged with the evolving safety and anticancer activity profile of oral fadra's monotherapy. Importantly, this anticancer activity has been observed during the Phase I dose escalation stage, which typically that treats all comer sicker patients who have received multiple prior therapies. Ordinarily, we don't expect to see much or any significant evidence of clinical benefit in such a heavily pretreated Phase I population.

Initial observations of oral fadra activity as a single agent dose daily build on those in a prior clinical study, which dose fadra intravenously, albeit with a suboptimal dosing schedule. These included a patient with heavily pretreated MCL1 amplified endometrial cancer, who achieved a confirmed complete response after initially achieving partial response. This patient remains on study after more than 2.5 years of treatment. The 065-101 study of oral fadra continues to enroll very well at 4 U.S., South Korean and Spanish sites and is on track to establish recommended Phase II dose or RP2D within 2022.

We anticipate starting the Phase II stage of this study shortly after RP2D. Dr. Mark Kirschbaum, our Chief Medical Officer, will provide further details on this study and our other programs. As clinical data with oral fadra in 065-101 are starting to emerge, we're also encouraged by fadra's competitive attributes, particularly as we survey the next-generation CDK inhibitor landscape. Relative to other development stage CDK inhibitors, we believe that oral fadra has the potential for best-in-class thus far based on dual targeting of CDK2 and CDK9, very good tolerability at higher dose levels, a daily dosing schedule in preliminary anticancer activity in patients with lymphomas, endometrial and pancreatic cancers.

We note that targeting CDK2 appears to be gaining more visibility as an important target for the biopharma industry. For example, Pfizer recently disclosed plans to advance its CDK2 inhibitor into a substantial Phase II study for the treatment of breast cancer, which clearly represents a sizable investment and a vote of confidence in the class. Notably, this Pfizer molecule does not inhibit CDK9. Data from Cyclacel's clinical studies show that patients with gynecological cancers often overexpressed multiple proteins that can be suppressed by targeting both CDK2 and CDK9. Hence, a dual inhibitor may have advantages over inhibitors that target a single enzyme. Our second clinical protocol designate 065-102 is evaluating oral fadra in leukemias or myelodysplastic syndromes and is now dosed in patients at dose level 4. 065-102 may provide further opportunity to differentiate fadra from other CDK inhibitors if it is effective in both solid tumors and blood cancers.

Let me also briefly mention our third protocol 140-101, which is actively enrolling patients with solid tumors and lymphomas in a streamlined Phase I/II trial of our oral PLK1 inhibitor, CYC140. We believe that preclinical and early clinical data generated thus far support the potential of CYC140 single-agent activity. Importantly, this molecule is differentiated from the only other PLK1 inhibitor in clinical development on several attributes. We will have more to report on this compound, including details of its mechanism of action at our upcoming R&D Day.

I'd like to now turn the call over to Mark, who will provide additional details on the fadra clinical development program and the rest of our pipeline. Mark?

Thank you, Spiro. I would first like to review preliminary results of the Phase I dose and schedule finding part of 065-101, given the promising safety and early efficacy results we are seeing. We have enrolled 17 patients thus far with no severe drug-related adverse events reported. Oral fadra has been well tolerated at all dose levels to this point. With regards to responses, although we are still in the dose finding portion of the trial with higher dose level study, we have already seen one patient with cutaneous T cell lymphoma or CTCL, achieved a partial response, or PR, as measured by the most widely used method to monitor CTCL known as modified SWAT or a modified severity weighted assessment tool.

At the current fifth level, which is 100 milligrams twice a day for 5 days, every week, over a 4-week cycle, 2 further patients are showing signs of clinical activity. A patient with a very aggressive form of T cell lymphoma achieved a 38% reduction in target lesions by PET scan during the first treatment cycle. A third patient with advanced endometrial cancer achieved stable disease, along with a 15% reduction in target lesions within the first treatment cycle. It is also noteworthy that a pancreatic cancer patient on dose level 4 achieved stable disease by confirmatory scan following 5 treatment cycles or approximately 5 months. This is a remarkable result in pancreatic cancer. It is notoriously difficult to treat.

Given the activity and safety of fadra, we plan to optimize dosing by evaluating up to 2 more dose levels to ensure that we do not miss any activity. This is supported by our preclinical models, which we intend to present at our upcoming R&D Day. As we are not seeing toxicity, all clinical investigators in the study have agreed that it would make medical and scientific sense to continue dose escalation with the current form of schedule. The 2 additional dose levels will follow the usual 3+3 design to determine the recommended Phase II dose or RP2D before we enter Phase II, where patients with defined tumor tests will be treated with the primary objective of response to treatment.

Based on the streamlined design of our trial, once the dosing schedule are established, we will enter directly into the Phase II stage, which is designed with the appropriate biostatistics to allow discussions with regulatory authorities in the event of continued activity in tumor types. The tumor types, we focus upon on Phase II will reflect Phase I experience as well as extensive preclinical work by the company and by several of our investigators, and we'll also consider indications of unmet medical need that may lead to an accelerated approval of the synergy.

We are also testing oral fadra in the treatment of leukemia and myelodysplastic syndromes in study 06-102. This study continues to enroll patients with City of Hope and MD Anderson Cancer Center. Based on good tolerability in 065-101, we recently introduced the protocol amendment in 065-102. That allows us to admit to level 2 and 3. We are now enrolling dose level 4, which we believe should shorten the time line for reaching RP2D. Similar to the solid tumor study, once RP2D is determined, the study will enter into proof-of-concept cohort stage, where fadra will be administered, both of the single agent and in combination to patients who have the 7 cohorts relevant to the new drug's mechanism of action and informed by the clinical activity of fadra in previous studies. Single agent cohorts will include patients with acute myeloid leukemia or myelodysplastic syndrome, who have an inadequate response or progressed on venetoclax combinations with hypomethylating agent or low dose therapy.

We will also enroll a cohort with relapsed/refractory AML or MDS lesion with the 3 KIT or MAP kinase pathways, including N and K RAS, BRAF, PTPN11 and NF1. The trial will also include patients with CLL who have progressed after at least 2 lines of therapy, including a BTK inhibitor and venetoclax. In April, we are pleased to announce the publication in the journal, Leukemia that confirmed fadra's ability to suppress MCL1 and synergize with venetoclax in CLL. Results from the preclinical study confirmed that fadra inhibited CDK9-mediated transcription, reduced levels of the short-lived anti-apoptotic protein MCL1 and induced apoptosis in primary CLL cells.

To repeat the earlier routine, these data highlight the importance of continued treatment to prevent recovery of MCL1 protein level. Importantly, fadra combined synergistically with the BCL2 antagonist, venetoclax, demonstrated even greater synergy when targeted against 17p deleted CLL cells which were not sensitive to either agent alone. During the second quarter, we also made important progress in anti-novel-PLK1 inhibitor, CYC140 into a Phase I/II study for the treatment of solid tumors and lymphoma. Similar to the 2 fadra protocols, 140-101 is a registration-directed study now enrolling patients in Phase I dose escalation at City of Hope and MD Anderson Cancer Center with 2 further overseas centers ready to enroll patients.

We are encouraged with the drug's performance in the clinic thus far, having observed no dose-limiting toxicities. With respect to early signs of activity, 1 ovarian cancer patient with metastases have achieved stable disease with tumor shrinkage after the first treatment cycle and is continuing on treatment after 3 cycles. As previously mentioned, we plan to hold an R&D Day in the fall, at which we intend to provide a comprehensive update on both the oral fadra and oral CYC140 clinical programs in patients who have received multiple treatment cycles and higher doses, as well as the preclinical work that has been done by Cyclacel and our collaborators.

Given the importance of demonstrating on-target activity, we have made it a high priority of Cyclacel to develop collaborations with outside research groups to further inform us on the molecular pharmacokinetic and biologic properties of fadra and CYC140. This should be an exciting event as it will highlight the unique competitive attributes of fadra and CYC140 in their respective classes.

I will now turn the call over to Paul.

Thank you, Mark. As of June 30, 2022, cash and cash equivalents totaled $29.1 million compared to $36.6 million as of December 31, 2021. The company estimates that available cash resources will fund currently planned programs into the second half of 2023. Research and development or R&D expenses were $4.2 million for the 3 months ended June 30, 2022, as compared to $4.1 million for the same period in 2021.

R&D expenses relating to fadra were $2.6 million for the 3 months ended June 30, 2022, as compared to $2.8 million for the same period in 2021 due to increased clinical trial costs of $0.5 million associated the clinical trial evaluating fadra in Phase I/II studies offset by a reduction of $0.7 million in nonclinical expenditures. Additionally, R&D expenses related to CYC140 were $1.5 million for the 3 months ended June 30, 2022 as compared to $1.1 million for the same period in 2021 due to clinical trial costs associated with the start of the CYC140 Phase I/II study.

General and administrative expenses for the 3 months ended June 30 of 2022 were $1.6 million compared to $2 million for the same period last year due to a decrease in facilities, professional and recruitment costs. United Kingdom research and development tax credits were $1 million for each of the 3 months ended June 30, 2022, and June 30, 2021, and are related to qualifying R&D expenditure. Net loss for the 3 months ended June 30 of 2022 was $4.6 million compared to $5.1 million for the same period in 2021.

Operator, we're now ready to take questions.

(Operator Instructions) And our first question will come from Ahu Demir with Ladenburg Thalmann.

My first question will be about the R&D base. What are the plans to disclose at R&D day? Do we expect to see any safety data from fadra program? And I do have a follow-up question after that.

Yes, of course, we will show an update of current data, including any maturity we have from patients enrolled subsequently to the midyear announcement during the R&D Day and which should be in the middle of Q3 period.

That's helpful. Another question I have, Spiro is, we do -- do you see any synergistic toxicity inhibiting CDK9? Are there anything part to that causes the synergistic toxicity there?

Maybe, it's a question for Mark.

We haven't seen toxicity at all in the study so far. So hopefully, we'll stay that way.

That's okay. My last question is on the PLK program. You are assessing public tumors as well as key malignancies, and we have seen some data from other programs PLK program -- PLK1 program. I am curious if there's a particular indication you think there is a higher chance for 140 to be successful or you're more excited about? I would love to know about that as well.

Well, that's a great question, and we would like to know more answers we go further in the clinic. We're still in dose escalation much earlier than the fadra program. But we have disclosed our target indications for Phase II, which are based on a variety of factors, including the preclinical results and suitability of the target. And as you can see, these are bladder cancer, lung cancer as well as hematological tumor as we mentioned earlier, including some lymphomas. Of particular interest, of course, to many investors following the PLK1 space with KRAS in colorectal cancer, and we're excited to see that perhaps in the early stages of our Phase I program we might see colorectal patients based on the sites we have included in our trial. So it's still very much work in progress, but there are several indications not include in the other company's program that we intend to pursue as part of our Phase II program.

Our next question comes from Kumar Raja with Brookline Capital.

I'm [Shubhendu] for Kumar. So with regards to the CYC140 dosing, you had mentioned earlier about initiating in the single-digit milligram range. So what kind of those levels have you been able to test and how does that look so far?

Shubhendu, the question about 140, right?

Yes. Yes.

Okay. Thank you. I'll ask Mark to answer the question about the starting dose level and where we expect that to top out.

Yes. We're still early in that trial. So we're still in the low dose ranges. We're following it with PKs, and we will set to move forward. But even at the low dose level, we're starting to see some activity because we have this published preclinical data that suggests that low-dose continuous dosing with this drug may also have another form of clinical activity. And we've sort of seen that now. So that's kind of where we are right now in the trial. It's still early and we'll be continuing to go upward.

I hope that answers your question.

Yes, yes, it does. And my follow-up question would be, so could you talk a little bit about the enrollment in the 140 trial and are both solid and liquid cancers are they enrolling at the same rate? I think we had earlier talked about issues with enrollment in liquid cancers. So any color on that would be useful? And are you planning to activate in your regional sites other than the MD Anderson and City of Hope. Thank you.

What trial you are asking about?

140. Shubhendu asked about 140 solid tumor and then future plans for leukemia.

In 140? Yes. I think, again, 140 is very early. So it's important to us first to figure out the dose and schedule. And when we -- as we get closer to that, I think then we will activate the leukemia part of the study. So now the focus is on solid tumors and lymphomas, which we successfully grouped together in the fadra trial as well. It turned out to be a good idea. And we're doing it in the 140 program as well.

(Operator Instructions) Our next question will come from Jonathan Aschoff with ROTH Capital Partners.

I was wondering if you could help us understand what conferences we might be seeing some data at things where you put a place card abstract or something that makes you reasonably sure we'll have stuff at that with those conferences.

Jonathan, I think you're asking a question about whether we have plans to present data at upcoming conferences. Is that correct?

Yes. Which ones in particular, and if you've submitted any place holding abstracts or have any other reasonable surety that we'll see data at that or those conferences?

Right. We have submitted an abstract in an upcoming medical conference in oncology. This is later in the year. We do not know yet if our abstract was accepted. As you may be aware, there are various conferences that have different rules about updating placeholders, some didn't allow placeholders anymore. Some do. At this point, we expect to provide updated data sometime in the middle of the second half, probably after R&D Day as shown that the abstract is accepted. And then we'll follow-up, of course, in 2023 with follow-on submissions. But there will be at least one presentation if accepted this year.

Okay. At least one.

(Operator Instructions) We have no further questions at this time. I would like to turn the call back over to Mr. Rombotis for any additional or closing remarks.

Thank you, operator, and thank you, everyone, for joining Cyclacel's second quarter earnings Call. We're excited by fadra's safety, tolerability and observations of anticancer activity in the ongoing solid tumor study and the momentum of enrollment. We anticipate building even more momentum as the fadra solid tumor trial advances along with the other 2 clinical stage programs. The data we have generated thus far would not have been possible without the support of our dedicated physician collaborators and their teams and above all, the patients and their families. Our mission at Cyclacel is to develop innovative therapies that address some of the most difficult-to-treat cancers. We look forward to providing further updates on our progress in the second half of the year. Operator, at this time, you may end the call.

On behalf of our clients, I would like to thank you for joining. This concludes your program.