Cyclacel Pharmaceuticals Inc. Q1 2023 Earnings Call

Speaker 1: To all sides on hold, we do appreciate your patience in holding. We ask that you please continue to hold. Your conference will begin momentarily.

Speaker 1: Good afternoon and welcome to the Cyclist Cell Pharmaceuticals first quarter 2023 results conference call and webcast. At this time, all participants are in a listen-only mode.

Speaker 1: After today's call, members of the financial community will have an opportunity to ask questions.

Speaker 1: If you would like to ask a question at that time, please press star 1 on your telephone keypad. If at any point your question has been answered, you may remove yourself from the queue by pressing star 2.

Speaker 1: Lastly, if at any time during the call you should require operator assistance, please press or a star zero. bro.

Speaker 1: I would now like to turn the conference call over to the company.

Speaker 2: Good afternoon everyone and thank you for joining today's conference call to discuss microcell's financial results and business highlights for the first quarter of 2023. Before turning the call over to management, I'd like to remind everyone that during this conference call forward looking statements made by management

Speaker 2: are intended to fall within the safe harbor provisions of the Private Security's Litigation Reform Act of 1995 and Section 21-E of the Security's Exchange Act of 1934 as amended. As the fourth in our press release, forward-looking statements involve risks and uncertainties that may affect the company's business and prospects.

Speaker 2: projections and other forward-looking statements represent our judgment as of today. Encyclostyle does not take any responsibility to update such information.

Speaker 2: Finance and Chief Operating Officer in Dr. Mark Kirschbaum, Senior Vice President and Chief Medical Officer.

Speaker 2: Spiro will begin with an overview of our business strategy and progress. Mark will provide details on CycleSelves Clinical Programs, and Paul will provide financial highlights for the first quarter of 2023, which will be followed by a Q&A session.

Speaker 2: At this time is my pleasure to turn the call over to Spiro.

Speaker 3: Thank you, Grace, and thank you everyone for joining us today for our quarterly business update.

Speaker 3: We are on track to deliver key data readouts over the coming months from our two clinical programs. In the FADRA 065-101 study in patients with solid tumors and lymphoma, we are enrolling at those level 6A.

Speaker 3: pharmacokineric and pharmacodynamic data from this dose level suggest that we are achieving predicted target engagement levels on continuous dosing at the higher level.

Speaker 3: Using the optimal dose schedule is one of many parameters to increase the chance of success in phase 2.

Speaker 3: Among others, correlative analysis and translational data can confirm whether the observed drug effects are on mechanism together with learning on how to deal with toxicities observed in early development. At this point in the program, we feel encouraged that our clinical observations support??? are effective.

Speaker 3: presumed mechanism of action. The Phase 2 proof-of-concept or POC stage will consist of multiple cohorts defined by histology. We expect that cohorts may enroll at different rates.

Speaker 3: For example, it is possible that the fastest ones will be those in which we have already seen and they can't suractivity during the dose escalation stage.

Speaker 3: As previously reported, we have seen PRs and stable disease in patients with T7 lymphoma, women's cancers, including cervical, endometriol, and ovarian, and pancreatic cancer, all on FADRA monotherapy.

Speaker 3: Clinical data from this open label POC stage will be reported as they become available.

Speaker 3: When biotech companies enter negotiations for out licensing assets or a strategic exit, preparing the commercial drug product or DP is often kicked down the road to be dealt with by the next owner of the asset.

Speaker 3: Such an election can have a profoundly negative impact on valuation.

Speaker 3: As the timelines to launch become apparent to the licensee or purchaser. Mindful of these matters, the cyclosol team has been proactively investing in a tablet formulation of FADRA to replace the capsule currently used in clinical trials.

Speaker 3: A tablet VP has further advantages to capsules in terms of patient convenience and increased compliance.

Speaker 3: As a tablet, DP or FADRA has recently become available, we will treat a few patients with it within the phrase one part of our ongoing O65-101 study.

Speaker 3: We will provide further updates on this project as the emerge.

Speaker 3: Let us now turn to Ploggle.

Speaker 3: In our 140-101 study, we are evaluating logo in dose escalation stage as a treatment for patients with advanced solid tumors and lymphoma. We are currently dosing patients at dose level 4.

Speaker 3: Logo has previously shown early signals of anti-cancer activity at low dose levels.

Speaker 3: Inpatients with billy retract, nose muscle lung and ovarian cancer.

Speaker 3: Our preclinical program, aiming to elucidate PLOGO's differentiated biological profile, has revealed that, alongside the inhibition of PLK1, PLOGO has also demonstrated an epigenetic mechanism of action. This property may lead to a biomarker-driven clinical study in the future.

Speaker 3: Over the coming months, we expect key data readouts from the Phase 1-2 studies for FADRA and PLOGO.

Speaker 3: We expect to report complete dose escalation data with FADRA, followed by initial data from the FADRA Phase II PORC stage, which is expected in the second half of 2023.

Speaker 3: Those escalation in the blogger study continues and we expect to report initial data in mid to late 2023.

Speaker 3: from other molecules in their respective class with properties which may be best in class.

Speaker 3: I will now turn the poll over to Dr. Mark Kersbaum, our chief medical officer, to provide details on recent clinical data. Mark? Thank you, Fero.

Speaker 4: As you heard, both the phytoceglob and plegocertib clinical programs are progressing well, and are at important stages in their respective studies.

Speaker 4: Regarding FADRA, we are currently treating patients at dose level 6A, which is the final dose level at that line in the 065 101 protocol.

Speaker 4: In preparation for the upcoming start of phase 2, we are now introducing the tablet form into this dose level.

Speaker 4: Previously reported anti-cancer activity in the ongoing Phase I study should result in faster enrollment in certain tumor types.

Speaker 4: As we have reported, two out of three patients with T-cell lymphoma achieved PR, including a patient with a very aggressive, NGO-immuno-blastic form of peripheral T-cell lymphoma.

Speaker 4: 11 of 15 patients with cervical and demetrile liver and ovarian cancers achieved stable disease with target lesion reductions as their best response.

Speaker 4: A pancreatic patient maintains stable disease for five cycles of treatment. These are promising responses for this state of clinical testing and may predict deeper responses in Phase 2. Speaking of Phase 2 stage of 06-5101, most of our additional sites, including top sites in the US, Europe and Asia are now open.

Speaker 4: Together with our four phase one site, around 10 centers are ready to participate in the proof of concept stage in what will be a global study.

Speaker 4: The primary objective of the upcoming Phase II stage is to assess FIIR's activity and safety in relevant tumor types.

Speaker 4: The design of this registration directed study allowed us to recruit different tumor types and discrete cohorts, each running in parallel and independent of each other.

Speaker 4: Let's now turn to our second program with Plogocertib, our oral PLK1 inhibitor, currently in 140.101, a phase 1, 2 study in patients with advanced solid tumors and lymphoma.

Speaker 4: Published through clinical evidence suggests that LODOS continuous administration may be an effective strategy for PLK-1 inhibitors as well as the standard high dose Pulse-type strategy.

Speaker 4: In 141-01, we have observed intriguing clinical activity at the lowest doses of pogo given continuously. These included stable disease at dose level 1 in two patients.

Speaker 4: One with non-small cell lung cancer for eight cycles, and one with ovarium cancer for five cycles respectively.

Speaker 4: and at dose level 2 in a patient with billary cancer for three cycles. We are currently enrolling at dose level 4 and have seen no FAAs thus far.

Speaker 4: What we can say at this point is that Pogo is an active BRD-4 inhibitor and there appears to be a broader epigenetic story. 141-01 is designed to target several important tumor types where preclinical models and biology suggest single-agent activity, including colon cancer, lymphoma, and small cell lung cancer among others. Our study is designed to efficiently evaluate both dose and schedule to optimize RP2D for the proof of concept or cohort stage of the study.

Speaker 4: We look forward to updating you as we progress our evaluation of FADRA and PLOGO.

Speaker 4: I will now turn the call over to Paul to review our first quarter and financial results. Thank you Mark.

Speaker 3: Last week we announced receipt of $3.9 million or $4.7 million as a research and development or R&D tax credit from HMRC, the tax agency of the United Kingdom.

Speaker 3: The tax credit is for R&D costs incurred during the year ended December 31st, 2022, and is the amount disclosed on the income tax benefit line of the Statement of Operations.

Speaker 3: For the first quarter of 2023, the R&D credit is estimated at approximately $1.3 million.

Speaker 3: This R&D tax credit is an important source of non-dilutive capital, and we anticipate receiving the 2023 tax credit in early 2024.

Speaker 3: Proformer cash and cash equivalence total $16.1 million, comprised of the R&D tax credit of $4.7 million, and cash and cash equivalence as of March 31, 2023, or 11.4 million.

Speaker 3: Cash and cash equivalents as of December 31st, 2022 was 18.3 million.

Speaker 3: Netcash use and operating activities was $6.9 million for the three months ended March 31st, 2023, compared to $6.8 million for the same period of 2022.

Speaker 3: The company estimates that its available cash will fund currently planned programs into the first quarter of 2024.

Speaker 3: R&D expenses were 5.7 million for three months ended March 31, 2023, as compared to 5 million for the same period in 2022. R&D expenses relating to Father Cyclib were 4.1 million for the three months ended March 31, 2023, as compared to 3.6 million for the same period in 2022.

Speaker 3: General and administrative expenses for the three-month-centred March 31st, 2023 and 22 remain relatively flat at 1.6 million. Total other income net for the three-month-centred March 31st, 2023 was 0.2 million compared to an income of 1.3 million of the same period of the previous year. The decrease of 1.1 million for the three-month-centred March 31st, 2023 is primarily related to royalty income received in the prior. Net loss for the three-month-ended March 31st, 2023 was 5.8 million.

Speaker 1: You may remove yourself from the queue at any time by pressing star two. Once again, that is star and one to ask a question. Our first question comes from who? Demir with Latinburg Falman. Good afternoon. Thank you for taking my question. I'm congrats on the development. I just have two questions. First one is on the ethical fit from what are we expecting to see in terms of data from both HADRA and PLK-1 programs in terms of number of patients. What can you tell us in terms of the expectations what we are expecting to see?

Speaker 5: Hello, Ahu. Thank you for your question. I think we should consistently, as we have been saying, for some time now, report data from the Phase I study of FADRA. And Nassample Size will be around 25 patients.

Speaker 5: That's what I mean, the enrollment continues. We have seen up to now. We should be reporting both our recommended phase to those decisions, as well as PK and PD analysis, in particular on the relevant protein targets from a dynamic activity, as well as some translational data that has been generated by both the company and collaborators. For Plogal, we think the initial data set will appear towards the fourth quarter of this year.

Speaker 5: and enrollment remains robust. So it could surprise to the upside, but within conservatively fourth quarter. Finally, we expect to report initial data from the phase two cohorts of FADRA, or 65 101, probably the one of the year that of course depends on which cohorts enroll first.

Speaker 5: We've consistently expected that those that have seen previous activity, which have been FOMOCO or HORTS and Women's cancers, will enroll first. So these are the likely datasets we'll report this year.

Speaker 4: I think there's a question for Mark. Mark, would you like to take this? Yes, sure. So we've previously disclosed we had incidents of hyperglycemia in patients who had underlying issues with sugar control in the past. Those have been well treated with insulin and other such treatments. That may be an on-target effect of the same way that it's active in the women's tumors and other such things. And we had a bit of an issue with nausea, which we believe the introduction of the tablet may abrogate.

Speaker 4: the dose that we, the safety of this drug was even more than we anticipated and we got the higher doses than we initially conceived so we were giving a lot of capsules.

Speaker 4: So now with the introduction of proper tablets, we think that will be resolved. But other than that, we have on FODRA, we have no other consistent SAEs of high grade or even low grade, frankly. And with PLK1, the doses that we are at now, we are seeing a lot of changes in the

Speaker 4: we have not seen any SAIs at all. So both drugs are doing very nice on the safety front.

Speaker 6: Thank you, Mark. Thank you, Spira.

Speaker 6: Thank you, Mark. Thank you, Spira. Thank you, Aho.

Speaker 4: And we believe that this may provide a good way of treating multiple tumor types in a safe way. So we escalate both of these in an alternate fashion as we go into higher doses of the drug.

Speaker 7: Okay, thank you. And with 140, what do you think about maybe possible combinations with target therapies like RASDRAC inhibition or maybe even immunotherapies? Again, there's a question from Mark, please. Yeah.

Speaker 4: I believe that's an excellent question. It's a little early to disclose all that. I can tell you that we're aggressively pursuing all of these fronts in our preclinical work. So we have a very deep profile of preclinical work with some major investigators looking at many of these possibilities. Or say that...

Speaker 4: What we're able to do with this low dose continuous dosing is really sensitize a lot of types of therapy without incurring the severe toxicity that were seen at high doses when in the way that the drug was given in the past.

Speaker 5: the order of development, but these things will happen in that order not simultaneously.

Speaker 7: Thank you very useful. Thank you so much.

Speaker 7: Very useful. Thank you so much. Thank you, Shubhant.

Speaker 1: Thank you. At this time, there are no further questions in queue. I'll turn the call back over to Mr. Ram-Botus for any additional or closing remarks.

Speaker 5: As a reminder, our upcoming key milestones for 2023R report final data from dose escalation stage and RP2D determination from the O6-5-101 study of oral FADRA in patients with advanced solid tumors and lymphoma. First patient dosed with oral FADRA in Phase 2 proof of concept stage of O6-5-101 study in patients with advanced solid tumors and lymphoma.

Speaker 5: Report Phase I data from 140-101 study of oral plago in patients with advanced sort of tumors and lymphoma, and report interim data from initial cohorts in Phase II proof of concept stage of O65-101 study of oral fodra in patients with advanced sort of tumors

Speaker 5: 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.

Speaker 1: This concludes today's call. Thank you for your participation. You may disconnect at any time.