Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) Q4 2021 Results Conference Call March 28, 2022 4:30 PM ET
Company Participants
Spiro Rombotis – President and CEO
Paul McBarron – EVP, Finance and COO
Dr. Mark Kirschbaum – SVP and Chief Medical Officer
Conference Call Participants
Kevin DeGeeter – Oppenheimer
Ahu Demir – Ladenburg
Jonathan Aschoff – ROTH Capital
Kumar Raja – Brookline
Operator
Good afternoon, and welcome to the Cyclacel Pharmaceuticals Fourth Quarter and Full Year 2021 Results Conference Call and Webcast. [Operator Instructions] Please note, today’s call is being recorded. I would now like to turn the conference call over to the Company.
Unidentified Company Representative
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.
Spiro Rombotis
Thank you, John [ph], and thank you, everyone, for joining us today for our quarterly and full year business update.
As we’re all dedicated to helping patients in need, we are distressed to see innocent lives sacrificed, cancer patients denied care and hospitals destroyed in the Ukrainian conflict. We therefore add our voice to many others in our industry to urge our government to continue its efforts to mediate a ceasefire and allow humanitarian assistance to reach desperate people caught in the war zone.
Let us now turn to our reports. Before describing our progress with fadraciclib and CYC140, I wish to say how proud I am of the Cyclacel team and our collaborators. Against the backdrop of the continuing pandemic and recent geopolitical turmoil affecting biopharmaceutical operations globally, we have executed well in 2021 and achieved our clinical and corporate objectives. As a result, we are now positioned to reach important milestones, including reporting clinical data in 2022.
Let us now review the fadraciclib or fadra program. In the third quarter of 2021, we initiated 065-101, a Phase I/II study of oral fadra in advanced solid tumors and lymphomas. We have now dosed 12 patients in the first 4 dosing levels or DLs. We have moved quickly through dose escalation as fadra has been well-tolerated at each dose level with no dose-limiting toxicity observed thus far. The last 9 patients in this study had taken fadra by mouth twice daily for 5 days a week for 3 weeks out of a 4-week cycle. In DL4, fadra is given orally at 100 milligrams.
In terms of total dose, this is similar to the total dose at which durable partial response and subsequently complete response was observed in an MCL1-amplified endometrial cancer patient enrolled in the 065-01 study of fadra administered intravenously. We believe that effectiveness of apoptosis-enabling CDK inhibitors will mainly depend on achieving durable target suppression.
We believe that based on available information, fadra is the only drug in the class of apoptosis-enabling CDK inhibitors to have achieved daily dosing by the oral route and single-agent activity in patients with solid tumors. This may be important as venetoclax, the only FDA-approved apoptosis enabler, is also dosed daily by mouth.
Enrollment in 065-101 has progressed well, with City of Hope and MD Anderson Cancer Center recruiting patients thus far. Recently, 2 major cancer centers in Asia and Western Europe have joined the study. The Seoul National University Hospital and Vall d Hebron University Hospital in Barcelona were selected for their expertise with tumor types of interest. The Korean site, led by [Dr. Dyo], is widely known for hepatobiliary, also known as cholangiocarcinoma or biliary tract cancers; and the Spanish site, led by Dr. J. Tabernero, for colorectal cancer.
In addition to the initial 4 sites enrolling in the dose escalation stage of the study, we are in discussions with several other U.S. sites to be brought into the proof-of-concept cohort stage. As a reminder, the 7 mechanistically relevant cohorts include patients with breast, colorectal, including KRAS mutant, endometrial and ovarian, hepatocellular and biliary tract as well as lymphomas. And a basket cohort will enroll patients with biomarkers relevant to the drug’s mechanism, including MCL1, MYC, cyclin E and KRAS mutant, regardless of histology.
The protocol allows for expansion of individual cohorts based on response, which may allow acceleration of the clinical development and registration plan for fadra. The primary endpoint of the dose escalation stage is the termination of recommended Phase II dose and is designed to rapidly assess safety and tolerability. As specific histologies and biomarkers of interest are not required in dose escalation, this stage is not designed to determine early efficacy of fadra. The protocol allows investigators to enroll patients with relevant tumors to fadra’s mechanism if it is in the interest of patients.
In November, we achieved the second key clinical milestone in the fadra program with the start of 065-102, our Phase I/II trial in patients with relapsed or refractory leukemias or myelodysplastic syndromes. As previously discussed, the rationale for testing fadra in hematological malignancies is based upon prior clinical activity and the drug’s mechanism of action through CDK2 and CDK9. We have dosed 2 patients to date in the dose escalation stage of this Phase I/II study.
As a reminder, both fadra trials have been designed as streamlined registration-directed studies that should enable us to efficiently determine the recommended Phase II dosing level and assess single-agent safety, tolerability and preliminary activity across multiple histologies. With both studies underway, we plan to report new clinical and preclinical evidence supporting the unique properties and therapeutic potential of fadra, firstly from 065-101 in solid tumor and lymphoma in the first half of 2022, followed by 065-102 in leukemia in the second half of the year.
Let me now turn to our second candidate, CYC140 and orally available PLK1 inhibitor. We recently announced that 140-101, a Phase I/II trial for the treatment of solid tumors, open for enrollment and is now recruiting patients. Consistent with our fadra study, this Phase I/II registration-directed trial will follow a streamlined design, beginning with a 3+3 dose escalation stage, to decide safety and recommended Phase II dose. Once this dose has been established, the trial will immediately enter into a proof-of-concept cohort stage using a Simon 2-stage design.
In this stage, CYC140 will be administered to patients in up to 7 mechanistically relevant cohorts, including patients with KRAS mutant colorectal cancer, plus a basket cohort which will enroll patients with biomarkers relevant to the drug’s mechanism.
Overexpression of PLK1 is known to be important in many types of cancer. Based upon the totality of the clinical evidence, we believe that CYC140 may show single-agent activity in relevant cancer types. We look forward to updating you once the study gets underway.
Having reviewed our clinical progress and the status of our programs and before turning over the call to Paul to review our financials, I would like to review our key upcoming milestones: 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.
Paul McBarron
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.
Question-and-Answer Session
Operator
[Operator Instructions] We’ll take our first question today from Kevin DeGeeter with Oppenheimer.
Kevin DeGeeter
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?
Spiro Rombotis
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?
Dr. Mark Kirschbaum
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.
Kevin DeGeeter
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?
Spiro Rombotis
Mark, that’s for you.
Dr. Mark Kirschbaum
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.
Operator
We’ll go next to Ahu Demir with Ladenburg.
Ahu Demir
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?
Spiro Rombotis
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.
Ahu Demir
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.
Spiro Rombotis
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?
Dr. Mark Kirschbaum
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.
Operator
We’ll go now to Jonathan Aschoff with ROTH Capital.
Jonathan Aschoff
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?
Spiro Rombotis
That’s a great question, Jonathan, and this is one for Mark since he has now extensive experience with the oral drug.
Dr. Mark Kirschbaum
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.
Jonathan Aschoff
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?
Dr. Mark Kirschbaum
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.
Jonathan Aschoff
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?
Dr. Mark Kirschbaum
Yes. One could always write an amendment if one needs one.
Jonathan Aschoff
Okay. But you would find that to be an unexpected thing in your…
Dr. Mark Kirschbaum
No.
Jonathan Aschoff
You don’t think you’ll be doing that…
Dr. Mark Kirschbaum
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.
Spiro Rombotis
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.
Jonathan Aschoff
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?
Spiro Rombotis
Sure. We have data on the first line. So Mark, please give Jonathan your view on the currently observed safety image of the drug.
Dr. Mark Kirschbaum
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.
Operator
[Operator Instructions] We’ll go now to Kumar Raja with Brookline.
Kumar Raja
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?
Spiro Rombotis
Right. Mark, would you take that for fadra, please, regarding combinations?
Dr. Mark Kirschbaum
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.
Spiro Rombotis
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.
Kumar Raja
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?
Spiro Rombotis
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.
Operator
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.
Spiro Rombotis
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.
Operator
This does conclude today’s program. Thank you for your participation. You may disconnect at any time.
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