Cyclacel Pharmaceuticals Q2 2023 Earnings Call Transcript

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Provided by Quartr
August 9, 2023

There are 7 speakers on the call.

Operator

Good afternoon, and welcome to the Cyclacel Pharmaceuticals Second Quarter 2023 Results Conference Call and Webcast. At this time, all participants are in a listen only mode. After today's call, members of the financial community will have the opportunity to ask questions. Please note today's call is being recorded. Would now like to turn the conference call over to the company.

Operator

Please go ahead.

Speaker 1

Good afternoon, everyone, and thank you for joining today's conference call to discuss Cyclacel's financial results and business highlights for the Q2 of 2023. Participants are in the call over to management, I would like to remind everyone that during this conference call, forward looking statements made by management participants are intended to fall within the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995 participants 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 participants are with the Securities and Exchange Commission, which include, among other things, our Forms 10Q and 10 ks. All of our projections and other forward looking statements represent our judgments as of today, and Cyclacao does not take any responsibility participants will be available to update such information. With us today are Spiro Lombardi, President and Chief Executive Officer Paul McBahn, Executive Vice President, Finance and Chief Operating Officer and Doctor.

Speaker 1

Mark Kirchbaum, Senior Vice President and Chief Medical Officer. Spiro will begin with an overview of our business strategy and progress. Mark will provide details on Cyclacel's clinical program and Paul will provide financial highlights for the Q2 of 2023, which will be followed by Q and A session. At this time, I would like to turn the call over to Spiro.

Speaker 2

Participants are ready for questions.

Speaker 3

Thank you, Grace, and thank you, everyone, for joining us today for our quarterly business update. Both clinical programs with fadraciclib or Fadra and plogosertib or Plogo are progressing well, and we are on track to deliver key data readouts over the coming months. We expect to report complete dose escalation data with FADRA and determination of the recommended Phase II dose or RP2D. And in the PLOGO study, dose escalation data and further elucidation of its novel epigenetic mechanism. Participants are in the FADRA 65-1 hundred and one study in patients with solid tumors and lymphoma, our immediate task is to determine the recommended Phase 2 dose or RP2D and we're very close to achieving this goal.

Speaker 3

Pharmacokinetic and pharmacodynamic data from the initial patients at this dose level suggest that we are achieving level above the predicted target engagement levels on our daily dosing. In addition to choosing RP2D, Another parameter that may increase the chance of success in Phase 2 is the selection of the histologies in which we may expect to see anticancer activity. As previously reported, we have seen PRs and stable disease in patients with T cell lymphoma, women's cancers, including cervical, endometrial and ovarian and also pancreatic cancer, all on FADRA monotherapy. Phase 2 sites have been selected with this in mind and they are ready to participate once we declare RP2D participants will be conducting a Phase 2 proof of concept or POC stage of the study. Clinical data from this open label POC stage will be reported as they become available.

Speaker 3

Based on the totality of data collected to date, we believe that Fadra's CDK twonine profile is differentiated from other molecules in its class in terms of safety and anticancer activity reported thus far. Of note, competitor recently disclosed that after a strategic portfolio prioritization, they have discontinued preclinical trials of their AZD4573 candidates. AZD4573 is a CDK9 inhibitor administered intravenously once a week. We believe that continuous pressure on CDK2 and CDK9 targets is required to enable apoptosis. Accordingly, Fadra is a CDK2nine inhibitor administered by oral tablets on a daily schedule.

Speaker 3

Let us now turn to Plovo. We are very excited that Plovo could emerge as a PLK1 inhibitor with novel epigenetic activity. In our 143-one hundred and one study, we are evaluating Toggle in circulating doses now at dose level 5 as a treatment for patients with advanced solid tumors and lymphoma. Has shown early signals of anticancer activity at low concentrations in patients with sir? Our preclinical program aiming to elucidate Plogo's differentiated biological profile have revealed novel epigenetic activity at low concentrations.

Speaker 3

If further data corroborate these findings will enroll in the future 1 or more patient cohorts selected on the basis of specific biomarkers.

Speaker 2

Participants are ready to

Speaker 3

take questions. I will now turn the call over to Doctor. Mark Kirschbaum, our Chief Medical Officer to provide details on recent clinical data. Mark? Participants are now ready to begin.

Speaker 4

Thank you, Spiro. As you heard, both the Fadra and PLOGO clinical programs are accruing well are in important stages in their respective studies. Regarding Fadra, we are completing enrollment at dose level 6A participants are in the range of 2nd. I would like to summarize what we have seen recently in the 65,101 study. Patients with heavily pretreated endometrial cancer in dose level 6A has documented tumor shrinkage after one cycle and is ongoing.

Speaker 4

We previously reported that 2 out of 3 patients with T cell lymphoma achieved PR, including a patient with very aggressive angioimmunoblastic form of peripheral T cell lymphoma. 13 of 19 patients with cervical, endometrial, liver and ovarian cancers achieved stable disease with target lesion reductions as their best response, a pancreatic patient maintains stable disease for 5 cycles of treatment. These are promising responses for this phase of clinical testing and may predict deeper responses in Phase 2. The major toxicities we have seen thus far continue to be nausea and hyperglycemia, which were manageable and reversible. The primary objective of the Phase due stage to follow the determination of RP2D is to assess Pfizer's activity and safety in relevant tumor types.

Speaker 4

The design of this registration directed study allows us to recruit different tumor types in discrete cohorts, each running in parallel and independently of each other. Participants will now turn to Flogo, our oral PLK1 inhibitor. In the 14,101 study of Flogo in patients with advanced solid tumors and lymphoma, we have observed intriguing clinical activity at these early low dose concentrations given continuously. These included stable disease at dose level 1 in 2 patients with non small cell lung cancer for 8 cycles and ovarian cancer for 5 cycles, at dose level 2 in a patient with biliary tract cancers for 3 cycles and at dose level 4 in the patient with adenoid cystic carcinoma for 3 cycles. We are currently enrolling dose level 5.

Speaker 4

No SAEs have been reported thus far. Preclinical data have shown that Plogo has an epigenetic mechanism. Term epigenetics refers to the way cells control gene activity without changing DNA sequence. Approved drugs with epigenetic mechanisms such as histone deacetylase inhibitors or hypomethylating agents typically work at low concentrations as opposed to chemotherapy and other traditional forms of cancer therapeutics. We are actively investigating this potential participants are in the range of 10,000,000 in the range of 10,000,000 in the range of 10,000,000 in the range of 10,000,000 in the range of 10,000,000 in the range of 10,000,000 in the range of

Speaker 2

10,000,000 in the range of 10,000,000

Speaker 4

in the range of 10,000,000 in the range of 10,000,000 in the range of 10,000,000 in the range of these include colon, lung cancer and lymphoma. Our study is designed to efficiently evaluate both dose and schedule participants are ready to begin the presentation to optimize RP2D for the proof of concept or cohort stage of the study. We look forward to updating you as we progress our evaluation of Fabra and PLOGO. I will now turn the call over to Paul to review our Q2 and financial results.

Speaker 3

Thank you, Mark. Participants are in the range of $1,200,000 compared to $18,300,000 as of December 31, 2022. Net cash used in operating activities was $8,200,000 for the 6 months ended June 30, 2023, compared to $8,700,000 for the same period of 2022. The company estimates that its available cash will fund currently planned programs will be recorded through the end of 2023. However, the operating plan includes discretionary expenditures, which if not incurred, could extend our liquidity requirements into the Q2 of 2024.

Speaker 3

Research and development or R and D expenses were $4,700,000 for the 3 months ended June 30, 2023, as compared to $4,200,000 for the same period in 2022. R and D expenses relating to FADRA were $3,000,000 for the 3 months ended June 30, 2023, as compared to $2,600,000 for the same period in 2022 due to increased non clinical expenditures. R and D expenses related to Plogo were $1,400,000 for the 3 months ended June 30, 2023, as compared to $1,500,000 for the same period in 2022, due to clinical trial costs associated with the progression of the 140-one hundred and one study. General and administrative expenses for the 3 months ended June 30, 20232022 remained relatively flat participants are at $1,600,000 Total other expense net for the 3 months ended June 30, 2023 was $100,000 compared to an income of $200,000 for the same period of the previous year. United Kingdom Research and Development Tax Credits for the 3 months ended June 30, 2023 were 600,000 research and development tax credits are directly correlated to qualifying research and development expenditure.

Speaker 3

Net loss for the 3 months ended June 30, 2023 was $5,400,000 compared to $4,600,000 the same period in 2022. Operator, we are now ready to take questions.

Operator

First question comes from Ahu Demir, Ladenburg.

Speaker 5

Hello. Thank you very much for taking my questions. Steve on our side. First one would be, given the recent developments and needs in the PLK1 field this week, Could you elaborate more on the differential profile of Plogo compared to other PLK1 inhibitors? I know mecanizumofaction will be disclosed later in time, but just curious

Speaker 3

There are 2 clinical stage PLK1 inhibitors, as you mentioned. The difference between Plovo and the other candidates is that we have an epigenetic mechanism as evidenced by cross reactivity with BRB-four have a validated epigenetic target, whereas the other molecule does not. Very importantly, our molecule has presumed single agent activity, which we have seen in several patients. At the same time, we believe that the etymology has never been tested in a single agent protocol has always been tested in combinations. Lastly, the developments of this week relates through a change in clinical trial plan to have the molecule in frontline of colorectal cancer.

Speaker 3

This is certainly a cancer of interest to us As is the potential KRAS mutation, but that is only a part of the story that will emerge when we disclose the full details of Plogo's epigenetic mechanism. Last point that I have found you to consider here is that both of these drugs were given orally. We have a potential best in class half life of around 11 hours versus about 24 without the molecule. We believe both molecules have a chance to make it to market, but we believe on different indications based on the very different biological functions.

Speaker 5

Thank you, Spiro. And a follow-up question would be, what are there any indications that you see a Greater efficacy or flugel when you're trying in the clinical trial.

Speaker 3

Well, it's still early days. As I think Mark reported, we have seen activity in 4 different tumor types in about a dozen or so patients so far. These are adenoid cystic carcinoma, obviously non small cell lung cancer, which is very exciting given of this market to any oncology new drug and also in ovarian and biliary tract cancers. So women's cancers remain of great interest to us for the reasons that we have seen before in this class as is the potential for activity in lung. We have not had any colorectal patients enroll so far that may change and that of course will change our picture will be the Valsha bladder cancer is sensitive to PLK1 inhibition and possibly triple negative breast.

Speaker 3

So it remains a story to unfold, but of course, what may matter here is that if the epigenetic mechanism of FOGO is fully corroborated, we could be able to enroll mutationally selected patients. In other words choose patients based on the mutation that is driving the tumor and enrolled a specific cohort with this type of patient profile that can sometimes be tumor agnostic regardless of the tumor tissue in which the tumor originated when we could enroll patients only because of the mutation. More on that in the next quarter as the story fully unfolds.

Speaker 5

Makes sense, Pio. And my last question will be when should we Any efficacy data from any of the programs, FADJOR or PLOGOV? When what does the time line look like?

Speaker 3

Well, the first report that we mentioned will be the full Phase 1 results for FADRA in the 5-one hundred and one study, this should come by the end of this year, possibly a bit sooner. You should be aware that there are extensive preclinical data have been worked on by collaborators of Cyclacel and the company itself that will complete the story of FADRA as you unfold in the clinic prior to us beginning Phase 2, which we're ready to go at this moment as soon as the last patients complete follow-up. In the case of FLOWGO, we will disclose the mechanism of this year, we expect data by the end of December, but of course, we need to have additional confirmation by acceptance of sponsored studies, which are in progress and expect to have the first clinical results for Plover early next year, conservatively assuming would take us at least 2 or 3 more cohorts calls before we complete those installation. So both of these products will have a data flow over the next 2 to 4 quarters.

Speaker 5

Sounds good. Thank you very much for answering my questions.

Speaker 3

Thank you, Rahul.

Operator

Our next question comes from Jeff Jones, Oppenheimer.

Speaker 6

Good afternoon, guys, and thanks for taking the questions.

Speaker 3

Alf? Just a couple of follow ups to

Speaker 6

Austin's on SPADRA. I just wanted to confirm for the dose level 6A that you need to call your RP2D. Do you have, 6 patients enrolled at this point? And how long Does it take from enrollment to be able to call RP-2D? And then from there, What does timing look like to start the Phase 2 POC study?

Speaker 2

Participants are ready for questions.

Speaker 3

Thank you for your question, Jeff. Let me ask Doctor. Keshbaum to answer the first part of the question, Mark, and then I'll come back can talk about Phase 2, one more complete. Any response to your question?

Speaker 4

Sure. We have the last two patients that consented

Speaker 3

So the time to achieve a P2D mark? At this time, we'll follow-up the protocol that Jeff has.

Speaker 4

So technically, the DLP period is 1 cycle. So If they get through 1 month in terms of safety, we could declare it. We'll still be following them for activity. Obviously, 1 month will be early for that, but the safety part of it is 28 days.

Speaker 3

Great. Thanks. Thank you, Mark. So as your second question was when are we ready to start Phase 2? Obviously, one prerequisite balance sheet and strategic options are available to the company right now.

Speaker 3

We obviously face a challenging capital markets environment, but there's a lot of in both of our drugs, which the company is keen to explore to understand alternatives to create so called value. So all of this time, I'm going to turn the call back to the call to the call to Mr. President. And as explained in his section of the prepared remarks,

Speaker 6

presenting the data on the dose escalation in the lymphoma solid tumor patients, so the totality of the Phase 1 data towards year end, are you thinking about that at a conference or a company sponsored event to walk through all that data, how are you thinking about that?

Speaker 3

Participants will be able to do both of the above. Obviously, the Fed lines past us for some of the conference at year end like Antonio or have you, therefore, we'll have to consider the company announcement first with our conference submissions for early 2020. Participants are ready.

Speaker 6

Thank you very much, guys, and congrats on the quarter.

Speaker 3

Thank you.

Operator

Our next question comes from Kempe Dovler, Brookline Capital Markets.

Speaker 6

Great. So with regard to discretionary spending, given where you are with the likely timing of data and your resources, what's the dollar amount of discretionary spending you're talking you're thinking about when you talk about extending the runway into Q2.

Speaker 3

I think this one is for Paul. Thank you, Ken. Thank you, Ken. Thanks, Gabriel. So I think that the what we would look at clearly is uncommitted expenditure at the moment.

Speaker 3

That's what we referred to by discretionary. I think the important fact is that by limiting some of that uncommitted spend, It allows us to bring in, in the early part of 2024, Ken, about $3,500,000 of the UK R and D tax credit. That's a significant cash flow into the company, which allows us to then extend into that Q2 2024 number that I mentioned in our prepared remarks.

Speaker 4

Got it. And

Speaker 6

not to focus too much on this, but FADRA still looks like the more interesting program over Plogo, if you had to make a choice. Is that fair?

Speaker 3

That is a fair question, almost as fair as asking a parent which of the 2 children they like the most. It's certainly the most advanced and has the most clinical data and it's an active compound with an excellent safety record. As we said in our prepared remarks, we had actually 2 competitors who seem to have lost momentum, if not terminating programs in the next generation CDK field, in our opinion, increase hardgrass scarcity value and potential equity value for stockholders. The other dimension of your question, Ken, that we should bring to the attention of investors, that there is a lot of interest in these compounds from strategics. And our interest can manifest itself in various corporate developments as well as alignments.

Speaker 3

Obviously, we need to explore those in due course in parallel to other initiatives and that will dictate which molecule could come forward the fastest. For example, if we were to theoretically out license Fadra, we could develop Plogo with non delivery funding coming from Fadra or the opposite. If parties became as excited as we are about the mechanism of action of Plogo, the inverse could happen and therefore non diluted capital from Plogo transactions could support FADRA. So, we are committed to taking both drugs forward at this time. Given that the spend is relatively modest to get to the end of Phase 1 for Ploego And to get Fadro Phase 2 ready.

Speaker 3

So I hope you understand that the company is exploring all available avenues to maximize stockholder value in this difficult time in the capital markets.

Speaker 6

Yes, that's clear. Thank you.

Speaker 3

Thank you for the questions, Kent.

Operator

We have no further questions in the queue at this time. I would now like to turn the call back over to today's speakers.

Speaker 2

Participants are ready to take questions.

Speaker 3

Thank you very much, operator, and thank you, everybody, for joining us today for our quarterly earnings call. Both of our programs are approaching important catalysts with a strong competitive profile in the therapeutic classes. As a reminder, our upcoming key milestones for 2023 are report final data from dose escalation stage participants are in the RP2D determination from the 65-one hundred and one study of Oral FODRA in patients with advanced solid tumors and lymphoma. 1st patient dosed with oral FODRA in Phase 2 proof of concept study of 65-1 hundred and one in patients with advanced solid tumor cell lymphoma, report Phase 1 data from 140,101 study of oral plover in patients with advanced solid tumors and lymphoma and elaborate novel mechanism of action of FLOWLOVO. We look forward to providing you with further elements and hope to meet you at upcoming conferences.

Speaker 3

Operator, at this time, you may end it.

Operator

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

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Key Takeaways

  • Both fadraciclib (FADRA) and plogosertib (PLOGO) clinical programs are progressing on schedule, with FADRA approaching RP2D determination and PLOGO dose escalation revealing a novel epigenetic mechanism.
  • Early Phase 1 data for FADRA show partial responses in T-cell lymphomas and stable disease in several solid tumors, with manageable toxicities (nausea, hyperglycemia), underscoring its differentiated oral CDK2/9 profile.
  • PLOGO has shown single-agent anticancer activity at low continuous doses in multiple tumor types, and preclinical studies confirm a unique epigenetic mode of action that will guide future biomarker-selected cohorts.
  • Cyclacel used $8.2 million in operating cash in Q2, holds enough cash to fund current programs through end-2023, and can extend its runway into Q2 2024 by reducing discretionary spending and tapping UK R&D tax credits.
  • Upcoming milestones include final Phase 1 results and RP2D announcement for FADRA, initiation of the FADRA Phase 2 proof-of-concept, and Phase 1 readouts plus detailed mechanism disclosure for PLOGO by year-end/early 2024.
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Earnings Conference Call
Cyclacel Pharmaceuticals Q2 2023
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