Good afternoon, and welcome to the Cyclacel Pharmaceuticals Fourth Quarter and Full Year 2021 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 fourth quarter and full year 2021.

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 Forms 10-Q and 10-K. These filings are 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 on Cyclacel’s clinical programs, and Paul will provide financial highlights for the fourth quarter and full year of 2021, which will be followed by a question-and-answer session.

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

first half 2022, dose first patients with oral CYC140 in the 140-101 advanced solid tumor study; initial data from Phase I dose escalation of the 065-101 solid tumor study of oral fadraciclib; second half 2022, enter Phase II proof-of-concept stage in the 065-101 solid tumor study of oral fadraciclib in 8 cohorts, 7 by histology and a basket cohort; initial data from Phase I dose escalation of the 065-102 leukemia study of oral fadraciclib.

I will now turn the call over to Paul..

Thank you, Spiro. As of December 31, 2021, cash and cash equivalents totaled $36.6 million compared to $33.4 million as of December 31, 2020. The increase of $3.2 million was primarily due to $21.7 million of cash provided by financing activities, offset by $18.5 million net cash used in operating activities.

The company estimates that available cash resources will fund currently planned programs through mid-2023. Research and development, or R&D expenses, were $4.6 million and $15.5 million for the 3 months and year ended December 31, 2021 as compared to $1.4 million and $4.8 million for the same periods in 2020.

R&D expenses relating to fadra were $3.4 million and $11.1 million for the 3 months and year ended December 31, 2021 as compared to $1.1 million and $3.7 million for the same period in 2020 due to clinical trial expenses for the evaluation of fadra in Phase I/II studies and clinical supply manufacturing.

Additionally, R&D expenses related to CYC140 were $1.1 million and $3.6 million for the 3 months and year ended December 31, 2021 as compared to $0.2 million and $0.6 million for the same period in 2020 as preclinical evaluation and clinical trial supply manufacturing of CYC140 progressed.

General and administrative, or G&A expenses, for the 3 months and year ended December 31, 2021 were $1.9 million and $7.5 million compared to $1.8 million and $5.9 million for the same periods of the previous year due to increased legal and professional and personnel costs and a lease assignment.

G&A expenses included noncash stock compensation costs of $0.1 million and $0.8 million for the 3 months and full year ended December 31, 2021 compared to $0.1 million and $0.3 million for 2020.

United Kingdom research and development tax credits were $1.2 million and $3.8 million for the 3 months and year ended December 31, 2021 as compared to $0.4 million and $1.2 million for the same periods in 2020 due to the increase in eligible R&D expenditure.

Net loss for the 3 months and year ended December 31, 2021 were $5.3 million and $18.9 million compared to $2.8 million and $8.4 million for the same periods in 2020. Operator, we are now ready to take questions..

We’ll take our first question today from Kevin DeGeeter with Oppenheimer..

Maybe 2 on the fadra solid tumor program. Spiro, how should we think about the scope of the medical meeting update in the first half of the year? How many cohorts of data should we hope to get some safety data on? And then just kind of help us put in context the guidance for opening up the Phase II expansion cohorts in the second half of 2022.

What does that suggest in terms of where you think you may ultimately land on dose escalation?.

Right. Thank you for that, and I will ask Mark to come and give his perspective on the specific dose, Kevin, but thank you for your question. First of all, let me explain a transition with regard to medical meeting.

It has become clear now that the relevant meeting that we were interested in presenting our data has changed their policy and we have to therefore use the original abstract in that meeting. We’re not allowed to update it for trials and progress. This is posted on the website, so we have to comply.

We therefore are thinking of a company announcement, possibly an investor event, around the similar time frame, midyear, in which we will put the data into the public record. We expect to have safety data per your question for all 12 patients that have been currently enrolled for the 4 dose levels that were mentioned in the prepared remarks.

And we may have scans for at least 9 of these patients, with some mature follow-up and possibly early scans, but unclear how mature for the last 3 on dose level 4. As for the second part of the question, what are the possibilities for the Phase II portion. We expect to start in the second half.

The medical team at Cyclacel have been busy speaking to a large number of primarily U.S. sites who are interested in participating. So I expect we should start smoothly.

We already have 4 sites open as you have heard, so we’ll get possibly up to 10 sites in total participating in the Phase II study to enroll patients in each of the 8 cohorts in the design.

Let me at this point ask Mark to give you his perspective about the rules in the protocol about the termination of RP2D and what his sense is of where we are in the activity range for the drug.

Mark?.

Yes. Thank you, Spiro. I think you covered the trial situation very well. The way the trial is designed is we go through essentially one more dose level, and then we have completed the trial. As is usual with these things, we will present to the FDA and all of that.

But the way the trial is designed is that we automatically roll into the Phase II once the Phase II recommended dose is achieved. So we’re pretty close. There will be full PKs and PDs that will be determined and completed and presented..

Great. And then maybe my second question, on 102.

And specific to the additional sites being opened up in Barcelona and in South Korea, for the solid tumor program, will those sites also be enrolling for the hematologic malignancy program 102 as well?.

Mark, that’s for you..

The current plans are to go to tumor sites where we believe they have the best efficacy for the tumor groups that we’re interested in. So clearly, the Seoul group and the Barcelona group have tumor types that are of central importance for our development plans.

The current plans for the hematologic malignancy trial, although these are always subject to change, is to remain in the United States..

We’ll go next to Ahu Demir with Ladenburg..

I will start with the 140 program. I’m curious how many sites are currently open.

And also, when should we expect interim data readouts?.

Thank you for your question, Ahu. At this point, we have 2 sites open in the 140 study, with the third site to open towards the midyear point. We expect to have initial data from this study approximately a year from first patient in, which is imminent.

We may have interim results to report at appropriate quarterly earnings calls in between, but of course, it depends on how fast we escalate. And that, at this point, is something that is open to question as we don’t have the same extensive experience with 140 that we had with fadra.

So caution is required as we step up, but it’s looking very good based on PK and PD modeling data, and we think we’re going to be starting very close to the active range from the get-go. So we’re encouraged and look forward to reporting the results once the escalation completes..

I also have a follow-up question on that. We have seen some preclinical data of the synergistic effect of -- sorry, with PARP inhibitors. Does the current design allow you to try combinations? And maybe if you could provide your perspective if you are considering some combinations and what makes sense..

This is a question for Mark, both in terms of the protocol, permitting or not, combinations, then what are the potential synergistic mechanism that one could consider together with a PLK1 inhibitor like 140.

Mark?.

Yes. The current strategy is based on trying to achieve single-agent registration first. That’s the primary goal. We think that’s achievable with these drugs.

There is, of course, a good time for starting to work on combinations, right from the beginning in terms of the preclinical work, and then when we haven’t achieved Phase II dose, that would be a good time to start considering combination strategies. But for now, the primary focus of these studies is on single-agent activity..

We’ll go now to Jonathan Aschoff with ROTH Capital..

And congrats on the progress. I was wondering, when you were saying how, at the 100 mg level, that you were approaching the doses that as an IV gave you that response in the MCL patient, I was just curious, can you remind us over how many doses did you compare IV to oral.

And was it always, of course, ignoring the oral delay to blood levels versus IV, was it very, very consistent oral and IV kind of regardless of the dose?.

That’s a great question, Jonathan, and this is one for Mark since he has now extensive experience with the oral drug..

Yes. Hi. That’s a very good question. Fortunately, the viability of the oral drug seems to be extremely good as it was presented in the past. It’s almost equivalent to the IV. So the current schedule is at a BID dose.

So when we say 100, that’s 100 BID, which is relatively close to where the -- to what the IV dose given twice a week was at -- in the endometrial patient. This, of course, is 5 days a week for 3 weeks out of 4. So we’re very excited about the current enrollment..

Okay.

And may I also ask, you sounded as if you were quite confident that the fifth dosing cohort would be enough information for you to have an RP2D and proceed to Phase II, did I hear that correctly?.

Well, that’s how the protocol is written at this time. So those are the predetermined levels that we have in the protocol. So in theory, when these are done, we will then go to the -- onto the Phase II. Of course, before that decision is fully finalized, when we see the PK and get all of that information together, but we’re pretty close..

Okay. So then -- what’s my next question here.

I mean suppose you’re not happy with the fifth dose level, can you proceed to higher doses in Phase I?.

Yes. One could always write an amendment if one needs one..

Okay. But you would find that to be an unexpected thing in your....

No..

You don’t think you’ll be doing that....

It’s not unexpected. We’re aware that, that may be a possibility. But so far, we’ve been very happy with the progress we’re making and with the way the lab results, et cetera, have been turning out..

Perhaps one thing I could add, Jonathan, to Mark’s answer, is that the way the protocol was written, remember, we’re dosing 3 weeks out of 4 weeks in the cycle. So if we’re happy with safety and are currently dosing level 4, we could always go to 4 out of 4 weeks of treatment, which means that we’re going to give it without a break.

That’s probably more likely than going up. And the reason with this is the history of this class of transcriptional CDK inhibitors that experience diminishing returns after a certain point of exposure with threshold. In other words, more drug is not necessarily better, it could be worse.

So for this reason, we’re more likely to go to a longer schedule not to go up in dose. But that, I hope, gives you a bit more color on our thinking..

Definitely. And lastly, you guys made a very brief comment about tox.

Can you talk any more about toxicity, particularly at the 75 and 100 mg BID doses?.

Sure. We have data on the first line. So Mark, please give Jonathan your view on the currently observed safety image of the drug..

So the determinant of safety in a Phase I trial like this is the rapidity in which you can go from dose level to dose level. We have not had to expand any of the dose levels. So, so far, there have been no drug-related toxicities significant to slow down the escalations through the dose levels..

We’ll go now to Kumar Raja with Brookline..

And congratulations on the progress.

With regard to the Phase II and the different combinations, how are you thinking about dosing there with regard to safety and efficacy?.

Right.

Mark, would you take that for fadra, please, regarding combinations?.

Sure. I mean it’s important to note, there -- we have a large number of tumor types that we believe may be sensitive to the drug, which would mean that the possibilities of combinations are very large. It’s a very extensive set of possibilities that we may have.

As I mentioned before, we are doing preclinical data to set ourselves up for some of these things. There are some obvious ones in today’s discovery environment. But we don’t have -- there’s no specific plans to launch anything until we have our Phase II dose in place. That’s the real determinant of where we can go after that..

Let me add one more thing, if I may, Kumar, to Mark’s reply, which is that we have the clinical data suggesting that fadraciclib and possibly other CDK2/9 inhibitors could potentially synergize preclinically with immuno-oncology drugs, like anti-PD-1, anti-PD-L1. And that is a possibility in the clinic.

But as Mark explained, we need to first see single-agent activity and then develop appropriate modifications of the current study because that is all within the current protocol, we don’t need to go to the FDA or IRBs to get approval, and then propose appropriate combinations in light of the available single-agent data.

Hope this gives you a little bit more color on our thinking..

Okay. And with regard to the leukemia study, it looks like the enrollment is comparatively slower compared to the solid tumor.

Is it just a factor of the number of sites you have onboard enrolling for the study? Or what are the factors driving the comparatively slower enrollment?.

That’s exactly correct. We’ve only opened City of Hope at this point. MD Anderson is only now coming onstream. So your estimate is correct. We expect enrollment to pick up in the second part of the year, with 2 sites open. And then possibly, we’ll have additional sites join the study, depending on the progressions of the escalation levels..

And it does appear that we have no further questions at this time. I would like to hand the call back to Mr. Rombotis for closing remarks..

Thank you, operator, and thank you, everyone, for joining Cyclacel’s fourth quarter earnings call. Our focus is to continue efficient execution of our business plan, building on our team’s accomplishments in 2021, with cash on hand to fund through our clinical and corporate milestones into mid-2023.

We’re looking forward to reporting soon a new clinical and preclinical evidence, supporting the unique properties and therapeutic potential of fadraciclib and eventually CYC140. Thank you for your time and support of our efforts to help cancer patients in need. Operator, at this time, you may conclude the call..

This does conclude today’s program. Thank you for your participation. You may disconnect at any time..