Cyclacel Pharmaceuticals - Q2 2024

Transcript

Operator (participant)

Please stand by. We're about to begin. 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 ended June 30, 2024. 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 Securities and Exchange Commission, which include, among other things, our Forms 10-Q and 10-K.

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. Brian Schwartz, Chief Medical Officer. Spiro will begin with an overview of our business strategy and progress. Brian will provide details on Cyclacel's clinical programs, and Paul will provide financial highlights for the second quarter of 2024, which will be followed by a Q&A session. At this time, I would like to turn the call over to Spiro.

Spiro Rombotis (CEO)

Thank you. And thank you everyone for joining us today for our second quarter 2024 business update. We are pleased to report on our progress with the precision medicine strategy for Fadraciclib or Fadra, our oral CDK2/9 inhibitor, which was highlighted at the ASCO annual meeting in June. Recruitment in the enriched cohort of our CYC065-101 phase 2 proof of concept study is going well. In this cohort, we're evaluating Fadra as monotherapy in patients with CDKN2A and/or CDKN2B chromosomal abnormalities, including deep deletions or loss of function. The hypothesis we are testing prospectively builds on preclinical evidence and the phase 1 clinical data presented at ASCO, which evaluated Fadra as monotherapy from an unselected population. Clinical benefit was observed in heavily pretreated patients with several tumor types, including endometrial, lung, ovarian, pancreatic cancer, and T-cell lymphoma.

Retrospective analysis suggests that this activity may be associated in part with alterations in certain tumor suppressor genes, specifically CDKN2A and/or CDKN2B. We believe that there is great unmet medical need and industry interest in the patient population identified by CDKN2A or B abnormalities, which are closely located on chromosome nine and are often co-deleted. CDKN2A gene deletions occur in several solid tumors, including bladder, breast, endometrial, esophageal, glioma, head and neck, hepatobiliary, lung, including squamous, melanoma, ovarian, pancreatic, and also in certain T-cell lymphomas. CDKN2B deletions occur in several solid tumors, including bladder, breast, cholangiocarcinoma, endometrial, esophageal, glioma, head and neck, hepatobiliary, lung, including squamous and mesothelioma, melanoma, pancreatic, and others. Based on currently available data, we believe that Fadra has a strong competitive profile in its therapeutic class.

We expect to report on initial clinical activity from the phase 2 proof of concept part of the study starting in the fourth quarter of this year. I will now turn the call over to Brian to review our progress and discuss some of our clinical results in the Fadra program. Brian?

Brian Schwartz (Chief Medical Officer)

Thank you, Spiro. As Spiro mentioned, we are recruiting well in the Fadra POC study, and I'm very encouraged by the enthusiasm of our clinical investigators about enrollment of patients with CDKN2A/B cohort. Based on the pace of enrollment, we anticipate reporting initial results from around a dozen patients by the end of 2024. We have also opened a second cohort, which is recruiting patients with T-cell lymphoma. This was based on phase 1 signals of activity, including partial responses in two out of the three patients with T-cell lymphoma. As we progress with the Fadra phase 2 study, let me summarize the data presented at ASCO and the rationale for our clinical strategy. The ASCO dataset included 47 patients from the phase 1 dose escalation part of the CYC065-101 study, evaluating different Fadra dosing schedules as monotherapy in unselected population.

Patients were heavily pretreated, having received a median of 4 prior lines of therapy... Fadra was generally well tolerated with good compliance between dose level 1 and 5. Dose level 5, or 100 milligrams twice daily, 5 days a week, 4 out of 4 weeks, was selected for the phase 2 proof of concept part of the study. There were no drug-related SAEs at this dose level. The most commonly reported treatment-related adverse events were nausea, vomiting, diarrhea, fatigue, and hyperglycemia. A total of 25 drug-related SAEs were reported in 8 patients. Most common were hyperglycemia in 4 patients, platelet count decrease in 3, and accidental overdose in 3. A total of 34 patients had measurable target lesions at baseline. 2 partial responses were reported in patients with T-cell lymphoma, one of whom had a CDKN2A loss.

A squamous non-small cell lung cancer patient with CDKN2A and CDKN2B loss achieved a 22% reduction in tumor burden at four weeks. In addition, clinical benefit was reported in two patients with endometrial cancer, one each with ovarian and pancreatic cancer. A retrospective analysis of previously treated phase 1 patients identified an endometrial cancer patient who achieved a complete response over three years of treatment in a previous intravenous Fadra monotherapy study and was found to have a CDKN2A, CDKN2B, and MTAP loss. Although the phase 1 hypothesis-generating data are limited and cannot be generalized, we believe that the data supports evaluating the two patient cohorts with specific cancer types in the phase 2 POC part of the study. We look forward to reporting initial data in the upcoming months. I will now turn the call over to Paul to review the second quarter results.

Paul McBarron (The Executive VP, Finance and COO)

Thank you, Brian. As of June thirtieth, 2024, cash equivalents total $6 million, compared to $3.4 million as of December thirty-first, 2023. Net cash used in operating activities was $3.6 million for the six months ended June thirtieth, 2024, compared to $8.2 million for the same period of 2023. Net cash provided by financing activities was $6.3 million for the six months ended June thirtieth, 2024, as a result of receiving approximately $6.3 million net of expenses from the issue of common stock and warrants under a securities purchase agreement. The company estimates that its current cash resources will fund planned programs into the fourth quarter of 2024.

Research and development, or R&D, expenses were $2 million for the three months ended June 30, 2024, as compared to $4.7 million for the same period in 2023. R&D expenses relating to Fadra were $1.5 million for the three months ended June 30, 2024, as compared to $3 million for the same period in 2023, due to a decrease in clinical trial and other non-clinical expenditures. R&D expenses related to plogosertib, our PLK1 inhibitor, were $0.5 million for the three months ended June 30, 2024, as compared to $1.4 million for the same period in 2023, due to a decrease in manufacturing costs and other non-clinical expenditures. General and administrative expenses remained flat at approximately $1.6 million for each of the three months ended June 30, 2024 and 2023.

Total other expenses and net were $0.1 million for each of the three months ended June 30, 2024 and 2023. United Kingdom research and development tax credits for three months ended June 30, 2024, were $0.4 million, compared to $6 million for the same period in the previous year and are directly correlated to qualifying R&D expenditure. Net loss for the three months, June 30, 2024, was $3.3 million, including stock-based compensation expense of $0.2 million, compared to $5.5 million, including stock-based compensation expense of $0.4 million for the same period in 2023. Operator, we are now ready to take questions.

Operator (participant)

Thank you, Mr. McFerran. Ladies and gentlemen, at this time, if you would like to ask a question, please press star one on your telephone keypad, and you may remove yourself from the queue at any time by pressing star two. Once again, that's star one for questions today. We'll go first to Ahu Demir at Ladenburg Thalmann.

Ahu Demir (Analyst)

Good afternoon. Thank you very much for taking my questions. We have couple. First question is, what is the enrollment target for the CDKN2A and CDKN2B program? And other part of the question is, what would be the, what are the scenarios for this program, and what would be the benchmark and success that you would consider based on the data that you plan to disclose in the second half of this year?

Spiro Rombotis (CEO)

... Oh, thank you for your question. I think this is for Brian. Brian, over to you.

Brian Schwartz (Chief Medical Officer)

Hi, Ahu. I'll say, so the first question is, it's a sort of a two-stage process. So stage one is to look at approximately 12-14 patients, where you need to see more than two responses, and then you would move on to the next phase of the study. So success for the first part would be at least two responses in the first 12-14 patients. I hope that clarifies. And the next phase will just be to confirm that those responses just confirm in a bigger cohort.

Ahu Demir (Analyst)

Yes, that's, that's helpful, Brian. And how many - From how many patients are you planning to show data in the second half of this year, and what is the target enrollment for this program?

Brian Schwartz (Chief Medical Officer)

Accrual has been good, and the patients required have been, you know, that we need, have been screened. So we anticipate that's why we're reasonably confident we'll be able to, you know, present at least just around 12 patients worth of response data by the end of the year. Just to remind everyone, we scan here every two months. So, you know, if we are already in August, it would be sort of two months for the first scan and two months for the second scan to get the efficacy data on that group.

Ahu Demir (Analyst)

If I could ask one more question, Brian, I think I would, I would refer that question to you as well. In terms of the alterations, is there any reason to think the loss of CDKN2A and CDKN2B would be more potent form instead of the mutations and other other alterations? Or it could be any of these, and with the data disclosure in the second half, would we be able to see what is the status of these different alterations?

Brian Schwartz (Chief Medical Officer)

You bring up a really interesting point in terms of, you know, the different either deletions or different mutations that are present. I think from what we've seen so far is we'll be able to get at least a feel from, you know, our old treated patients plus the new set, which would be way over 20-25 patients to see is there a specific alteration that's more sensitive to the drug? So, we'll get an idea. There are numerous different ones, and hopefully from that analysis, we'll be able to hone it down even a little bit more.

Ahu Demir (Analyst)

Great. Thank you so much for answering my questions.

Operator (participant)

Thank you. And just a quick reminder, ladies and gentlemen, star one, please, for any further questions today. And gentlemen, it appears we have no further questions this afternoon. Mr. Rombotis, I'll turn things back to you, sir, for any closing comments.

Spiro Rombotis (CEO)

Thank you, Bo, and our thanks to all of you for joining Cyclacel's second quarter 2024 earnings call. We have achieved key milestones for Fadra with multiple patients dosed in the phase 2 proof of concept stage and look forward to important catalysts in 2024. These include reporting interim data from initial cohorts in the phase 2 open label proof of concept stage of the 065-101 study with oral Fadra in patients with 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.

Operator (participant)

Thank you, Mr. Rombotis. Again, ladies and gentlemen, that will conclude Cyclacel's financial results conference call. Again, thanks so much for joining us, everyone, and we wish you all a great remainder of your day. Goodbye.