Good afternoon, and welcome to the Cyclacel Pharmaceuticals Second Quarter 2022 Results Conference Call and Webcast. . Please note, today's call is being recorded. I would now like to turn the conference call 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 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 program and Paul will provide financial highlights for the second quarter of 2022 which will be followed by Q&A session.

At this time, I’d 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 media updates on June 30, at which were 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 Phase ½ study for the treatment of solid tumors and lymphomas designated 065-101 065. Thus far, we have enrolled 17 patients in the dosage escalation part of the study reaching dose level five without dose limiting toxicity.

Based upon preliminary results in the first five dose levels with Fadra dose daily, we are highly encouraged with evolving safety and anti-cancer activity profile of all fadra’s monotherapy.

Importantly, this anti-cancer activity has been observed during the Phase 1 dose escalation stage, which typically treats all calmer, sicker patients who have received multiple prior therapies. Ordinarily, we do not expect to see much or any significant evidence of clinical benefit in such a heavily pretreated Phase 1 population.

Initial observations of all 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 the confirmed complete response after initially achieving partial response. This patient remains on study after more than two and a half years of treatment.

The 065-101 study of oral fadra continues to enroll very well at four US, South Korean and Spanish sites and is on track to establish recommended Phase 2 dose or RP2D within 2022. We anticipate starting the Phase 2 stage of this study shortly after our RP2D. Dr.

Mark Kirschbaum, our Chief Medical Officer will provide further details on this study in 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 surveyed 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 and higher dose levels, a daily dosing schedule and preliminary anti-cancer activity in patients with lymphomas, endometrial, and pancreatic cancers.

We note that targeting CDK2 appears to be gaining more visibility is an important target for the biopharma industry. For example, Pfizer, recently disclosed plans to advance its CDK2 inhibitor into a substantial Phase 2 study for the treatment of breast cancer, which clearly represents a sizable investments 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 genic illogical cancers, often over express 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 product or protocol designate 065-101 is evaluating oral fadra in leukemias or myelodysplastic syndromes, and is now dosing patients at dose level four. 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 1/2 trial over 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 1 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 regard to responses, although we're still in the dose finding portion of the trial with higher dose level still to study, we have already seen one patient with cutaneous T cell lymphoma or CTCL achieved the partial response or PR as measured by the most widely used method to monitor CTCL known as the modified SWAT or Modified Severity Weighted Assessment Tool.

At the current fifth dose level, which is 100 milligrams twice a day for five days every week over a four week cycle. Two 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 of target lesions within the first treatment cycle. It is also noteworthy that a pancreatic cancer patient on dose level four achieved stable disease by confirmatory scan following five treatment cycles for approximately five months.

This is a remarkable result in pancreatic cancer, which is notoriously difficult to treat. Given the activity and safety of fadra, we plan to optimize dosing by evaluating up to two 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 were 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 four week schedule.

The two additional dose levels will follow the usual three plus three design to determine the recommended Phase 2 dose or RP2D before we enter Phase 2, where patients would define tumor types will be treated with a primary objective of response to treatment.

Based on the streamlined design of our trial, once the dose and schedule are established, we will enter directly into the Phase 2 stage, which is designed with the appropriate biostatistics to allow discussion with regulatory authorities in the event of continued activity in certain tumor types.

The tumor types is to focus upon in Phase 2 will reflect Phase 1 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 strategy.

We are also testing oral fadra for the treatment of leukemia and myelodysplastic syndromes in study 065-102. This study continues to enroll patients at City of Hope and MD Anderson Cancer Center. Based on good tolerability in 065-101, we recently introduced the protocol amendment in 0651-102 that allows us to admit dose levels 2 and 3.

We are now enrolling dose level 4 which we believe shorten the timeline 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 as a single agent and in combinations to patients then up to seven cohorts relevant to the drugs 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 syndromes, who have an inadequate response or progressed on Venetoclax combinations with Hypomethylating agents, or low dose Ara C.

We will also enroll the cohort with relapsed refractory AML or MDS with FLT3, KIT or MAPK pathways including N and K RAS, BRAF, PTPN11, NF1. The trial will also include patients with CLL who have progressed after at least two lines of therapy including a BTK inhibitor and/or venetoclax.

In April, we're 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 fadraciclib inhibited CDK9 mediated transcription, reduced levels of the short-lived, anti-apoptotic protein MCL1, and induced apoptosis in primary CLL cells. To repeat earlier theme, these data highlighted the importance of continuous treatment to prevent recovery of MCL1 protein levels.

Importantly, fadraciclib combine synergistically with the BCL2 antagonist, venetoclax, and 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 advancing our novel PLK1 inhibitor, CYC140 into a Phase 1/2 study for the treatment of solid tumors and lymphomas.

Similar to the two fadra protocols 140-10 is a registration directed study now enrolling patients in Phase 1 dose escalation at City of Hope and MD Anderson Cancer Center, with two further overseeing centers ready to enroll patients. We are encouraged with the drugs performance in the clinic thus far, having observed no dose limiting toxicities.

With respect to early signs of activity, one ovarian cancer patient with metastases have achieved stable disease with tumor shrinkage after the first treatment cycle, and it's continuing on treatment after three 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 at Cyclacel to develop collaborations with outside research groups to further inform us on the molecular pharmacokinetic and biological 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 three 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 three 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 5 million associated the clinical trials evaluating fadra in Phase 1/2 studies, offset by reduction of $0.7 million in non-clinical expenditures.

Additionally, R&D expenses related to CYC140 were $1.5 million for the three 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 1/2 study.

General and administrative expenses for the three months ended June 30, 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 each of the three months ended June 30, 2022 and June 30, 2021, and are related to qualifying R&D expenditure. Net loss for the three months ended June 30, 2022 was $4.6 million, compared to $5.1 million for the same period in 2021. Operator, we're now ready to take questions..

And our first question will come from Ahu Demir with Ladenburg Thalmann..

Good afternoon. Thank you very much for taking my question. My first question will be about the R&D day. What are the plans to disclose that R&D day? Do we expect to see any safety data from the fadra program? And I do have a follow up question after that..

Hello, Ahu. Thank you for your question. Yes, of course it will show an update of current data including any maturity we have from patients enrolled subsequently to the mid-year announcements during the R&D Day event which should be in the middle of the Q3 period..

That's helpful.

Another question I have Spiro is do we -- do you see any synergistic toxicity inhibiting CDK2, CDK9, are there anything particular that causes a synergistic toxicity there?.

There is a question for Mark..

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

That sounds great. My last question is on the PLK program. You are accessing solid tumors as well hem malignancies and we have seen some data from other PLK programs, 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 as we go further in the clinic. We're still in dose escalation much earlier than the fadra program. We have disclosed our target indications for Phase 2 which are based on a variety of factors including preclinical results and suitability of the target.

And as you can see, these are bladder cancer, lung cancer, as well as hematological tumor you mentioned early including some lymphomas of particular interest of course, to many investors following the PLK1 space is KRAS in colorectal cancer and we are excited to see that perhaps in the early stages of our Phase 1 program, we might see colorectal patients based on the size we have included in our trial.

So still very much work in progress. But there are several indications not included in the other companies program that we intend to pursue as part of our Phase 2 protocol..

Our next question comes from Kumar Raja with Brookline Capital..

Hi. I am 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 it look so far?.

Shumbendu, the question about 140, right?.

Yes..

Okay, thank you. I'll ask Mark to answer the question about the starting dose level and the way 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 assess and move forward. But even at the low dose level, we're starting to see some activity.

Of course, 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're sort of seeing 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 dose upward. I hope that answers your question..

Yes, it does. And my follow up question would be so could we 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 earlier, you talked about issues with enrollment in liquid cancers.

So any color on that would be useful? And are you planning to activate any additional sites other than the MD Anderson and the City of Hope? Thank you..

Mark?.

What he is asking about?.

140, Shumbendu asked 140 solid tumor and then future plans for hem..

In 140, yes, I think, again, 140 is very early. So it's important for us first, to figure out the dose and schedule. And when we let -- as we get close to that, I think then we will activate the leukemia part of the study.

For 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..

Our next question will come from Jonathan Aschoff with ROTH Capital Partners..

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

Hello, Jonathan, I think you asked me 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 sure key that will 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 don'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 soon as 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 thank you very much..

Alright. We have no further questions at this time. So 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 safety, tolerability and observations of anti-cancer 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 two 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..

Ladies and gentlemen, this does conclude today's teleconference and webcast. We appreciate your participation. And you may disconnect at any time..