Q4 2021 Cyclacel Pharmaceuticals Inc Earnings Call

Okay.

Good afternoon, and welcome to the Cyclostyle Pharmaceuticals fourth quarter and full year 2021 results conference call and webcast. At this time all participants are in a listen only mode. After todays call members of the financial community will have an opportunity to ask questions. If you would like to ask a question at that time.

Please press star one on your Touchtone phone if at any point. Your question has been answered you may remove yourself from the queue by pressing the pound Keith and posing your question. We ask that you. Please pick up your handset to allow optimal sound quality. The company will also be accepting a limited number of questions submitted via email to the address I are at.

Cyclostyle Dotcom lastly.

Lastly, if at any time during the call you should require operator assistance. Please press star zero.

He's note today's call is being recorded I would now like to turn the conference call over to the company.

Yeah.

Good afternoon, everyone. Thank you for joining today's conference call to discuss cycle cells 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 21 E 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.

Sure.

All of our projections and other forward looking statements represent our judgment as of today and Cyclostyle does not take any responsibility to update such information.

With us today are Spiro Ramada's, President and Chief Executive Officer, Paul Mcferran, Executive Vice President Finance, and Chief operating Officer, and Dr. Mark Kirshbaum, Senior Vice President and Chief Medical Officer Spear.

Spiro will begin with an overview of our business strategy and progress on sickle cells 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.

Okay.

Thank you John 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 sacrifice cancer patients denied care and hospitals destroyed and 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 cease fire and allow humanitarian assistance. They reached desperate people caught in the war zone.

Okay.

Let us now turn to our report.

Before describing our progress with pod recyclable and see what see 140, but we used to say how proud I am of the <unk>.

Cyclostyle team and our collaborators.

Against the backdrop of the continuing pandemic and recent geopolitical turmoil.

<unk> biopharmaceutical operations globally.

We have executed well in 2021.

And achieved our clinical and corporate objectives.

As a result, we're now positioned to reach important milestones, including reporting clinical data in 2022.

Let us now review the fact recycling about foundry program.

In the third quarter of 2021, we initiated 065 dash one O. One at phase one class two study of <unk>.

Our far draw in advanced solid tumors and lymphomas.

We have now dosed 12 patients in the first four dosing levels Rds.

We have moved quickly through dose escalation as Farnborough has been well tolerated at each dose level with no dose limiting toxicity observed thus far.

The last 90 patients in the study and taken further by a mouse twice daily for five days a week for three weeks out of a four week cycle.

In D O four five brands 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 mcl, one amplified endometrial cancer patients.

All in the all six five dash, Oh, one study or <unk> 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 Padre as the only drug in the class of apoptosis, enabling CDK inhibitors to have achieved daily dosing by the all our routes and single agent activity in patients with solid tumors.

This may be important is about <unk>. The only FDA approved apoptosis enabler is also dose daily by mouth.

Enrollment in all six five dash one O. One has progressed well with city of hope and M. D. Anderson cancer center recruiting patients thus far.

Recently, two major cancer centers in Asia, and Western Europe have joined the study.

Same old National University Hospital involved they have Rone University hospital in Barcelona were selected for the expertise with tumor types of interest.

The Korean side led by Doctor D Y O is widely known for Hepatobiliary also known as Cholangiocarcinoma abelian attract cancers.

And the Spanish site led by Doctor J P Knab, our darrow for colorectal cancer.

In addition to the initial four sites enrolling in the dose escalation stage of the study we are in discussions with several other U S sites could be brought into the proof of concept cohort stage.

As a reminder, the seven mechanistically relevant cohorts include patients with breast colorectal, including K, Ras mutant endometrial and ovarian HIPAA to cellular and biliary tract as well as lymphomas.

And as a basket cohort will enroll patients with biomarkers relevant to the drug's mechanism, including Mcl, one Mick second E N K Ras 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 Sabra.

The primary endpoint of the dose escalation stage is the termination of a recommended phase II dose and is designed to rapidly assess safety and tolerability.

As specific histology and the Biomarkers of interest are not required in dose escalation. This stage is not designed to determine early efficacy of hard rock.

The protocol allows investigators to enroll patients with relevant to us the thought Rosemary commision. If it is in the interest of patients.

Okay.

In November we achieved our second key clinical milestone in the fiber program with the start of almost six five dash one or two.

Our phase <unk> trial in patients with relapsed or refractory leukemias or Myelodysplastic syndromes.

As previously discussed the rationale for testing five dry in Hematological malignancies is based upon prior clinical activity.

And the drugs mechanism of action, so with CDK too and city canine.

We have a dose two patients to date in the dose escalation stage of this phase one slash two study.

As a reminder, both fiber trials have been designed a 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 histology.

With both studies underway, we plan to report new clinical and preclinical evidence supporting the unique properties and therapeutic potential of Hydra. Firstly from 065 Dash one O one in solid tumor and lymphoma in the first half of 2022 followed by <unk>.

Dash, one or two in leukemia in the second half of the year.

Yeah.

Let me now turn to our second candidate see what see 140 and orally available P O K one inhibitor.

We recently announced that one four to dash one O. One a phase once last two trial for the treatment of solid tumors opened for enrollment and is now recruiting patients.

Consistent with our fibrous study this phase one class II registration directed trial will follow a streamlined design beginning with a three plus three dose escalation stage, the decided safety and recommended phase two dose.

Once this dose has been established the trial will immediately enter into proof of concept cohort stage using a Simon two stage design.

In this stage see what she won 40 will be administered to patients and up to seven mechanistically relevant cohorts.

Patients with <unk> mutant colorectal cancer across a basket cohort, which will enroll patients with biomarkers relevant to the drug's mechanism.

Overexpression of P. O K, one is known to be important in many types of cancer.

Based upon the totality of preclinical evidence, we believe that C. O S. C 140 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 it over the call to Paul to review, our financials I would like to review our key upcoming milestones.

First half 'twenty 'twenty to dose first patients with oral let's see what see 140 in the 140 Dash one O one advanced solid tumor study.

Initial data from phase one dose escalation of the O six five dash one O one solid tumor study of oral <unk> and recycling.

Second half 2022 .

Enter phase II proof of concept stage in the O six five dash one O. One solid tumor study of all sort of recycling in eight cohorts seven by histology in the basket cohort.

Initial data from phase one dose escalation of the OS X five dash, one or two leukemia study of oral side recycle it.

I will now turn the call over to Paul.

Thank you Spiro.

As of December 31st 2021, cash and cash equivalents totaled $36 $6 million.

Compared to $33 4 million as of December 31st 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.

Okay.

The company estimates at 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 three 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 Farnborough with $3 4 million and $11 1 million for the three months and year ended December 31 2021 as.

As compared to $1 1 million and $3 7 million for the same periods in 2020.

Judy clinical trial expenses for the evaluation of Farnborough in phase one two slash studies and clinical supply manufacturing.

Additionally.

R&D expenses related to C Y C $141 1 million and $3 6 million for the three months and year ended December 31, 2021 ask.

As compared to <unk> 2 million and <unk> 6 million for the same periods in 2020.

As preclinical evaluation and clinical trial supply manufacturing of C Y C 140 <unk> progressed.

General and administrative or G&A expenses for the three months and year ended December 31st 2021.

Well 1.9 million and $7 5 million.

Compared to $1 8 million and $5 9 million 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.

$1 million and $8 million for the three months and full year ended December 31st 2021.

Compared to point 1 million endpoint 3 million for 2020.

United Kingdom research and development tax credits, but 1.2 and $3 8 million for three months and year ended December 31 2021.

As compared to <unk> 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 three months and year ended December 31 2021.

$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.

And as a reminder, if you would like to ask a question. Please press star and one on your Touchtone phone you can remove yourself from the queue by pressing the pound key we'll take our first question today from Kevin <unk> with Oppenheimer. Your line is open.

Okay, great. Thanks for taking my questions, maybe two on the power draw.

Telecamera program, yes.

As for 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 you know.

Just kind of help us put it in context the guidance for opening up the phase two expansion cohorts in the second half.

2022 what does that suggest in terms of.

You know, where you think you may ultimately land on dose escalation.

Alright, Thank you for that and I will ask Marc to come and give his perspective on the specific dose Kevin but thank you for your question first.

First of all let me explain our transition with regard to medical meeting it has become clear now that they're out of a 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 were not allowed to update it for trials in 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 mid year, and which will put the data into the public record. We expect to have safety data for your question for all 12 patients that have been currently enrolled for the four dose levels that were mentioned in the prepared.

Remarks, and will May have scans for at least nine of these patients with some mature follow up and possibly early scans, but unclear how much sure for the last three on dose level four.

As for the second part of the question of what are the possibilities for the phase two portion we expect to start that in the second half by the medical team at cycle as it had been busy speaking to a large number of primarily U S sites were interested in participating so I expect that we should start smoothly. We already have four sites opened as you have heard so well.

Get possibly up to 10 sites in total, but dissipating or the phase two study to enroll patients in each of the eight cohorts in a design.

At this point ask Mark to give you his perspective about the rules in the protocol about the termination of RP two D and what the Houston says of where we are in the activity arrange for the drug.

Mark.

Thank you Joe.

I think you've covered.

The 12 situation very well.

The trial is designed as we go through.

Actually one more dose level and then we have completed the trial as is usual with these things we will we will present to the FDA and all of that but the way. The trial is designed is that we automatically roll into the.

Thanks to once the phase two recommended dose is achieved.

So we're pretty close.

Uh huh.

Both PK and PD is that will be that will be determined and completed and presented.

Oh, Great and then maybe my second question on on one O two and specific to the additional sites being opened up in Barcelona and in South Korea.

For the solid tumor program all those sites also.

Be enrolling for.

Yeah, the hematologic malignancy program.

Two as well.

Oh, that's for you.

Current plans are.

To go to tumor sites, where we believe.

They have the best efficacy for the tumor.

We understand that clearly.

So group into Barcelona group have tumor types.

So important for our development plan.

Current plans for the the hematologic malignancy trial. Although these you know these are always subject to change.

The remainder of the United States.

Great. Thanks for taking our questions.

Thank you Kevin.

We'll go next to get married with Ladenburg Your Atlanta line is open.

Thank you very much for taking my question.

I'll start with Moms 40 program I'm sure yet how many quite by trying to okay.

And also then should we expect interim data readout.

Thank you for your question of who at this point, we have two sites open in the 140 study with a third site to open towards the mid year point, we expect to have initial data from this study approximately a year from first patient in which is imminent.

May have interim results to reports at appropriate quarterly earnings calls in between because that of course depends on how fast we escalate and that at this point is something that is open to question is we don't have the same extensive experience with 140 that we had with Fabra. So caution is required as we step up but it's looking very good based on <unk>.

And P D modeling data and we think we're gonna be act as 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.

Thank you Spiro I always kind of a follow up question on that.

Some preclinical data of the synergistic effect of Oh, sorry.

Big PARP inhibitors, thus securing these line allow you to try combinations and maybe if you could provide your perspective, if you are considering some combinations and what makes sense.

There is a question for Mark both in terms of the protocol or permitting or not combination is then what are the potential synergistic mechanisms that one could consider together would that be okay. One inhibitor like 140 Mark.

Yes.

Geez.

It's based on trying to achieve a single engine legislation first.

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 the single agent activity.

Thank you thanks for taking my question.

Thank you Ivo.

We'll go now to Jonathan Aschoff with Roth Capital Your line is open.

Hi, Thanks, guys and congrats on the progress I was wondering when you were saying how at the 100 Meg.

Level that you were approaching the doses that as an IV gave you that response in the Mcl patients I was just curious can you remind us over how many doses did you compare IV to oral and you know was it always it of course, you know ignore any oral delay to all blood levels versus I D.

Was it very very consistent on I E kind of regardless of the dose.

That's a great question Jonathan of his one for Mark since he has now extensive experience with the oral drug.

Yes, hi.

All right good question Fortunately.

Oh really.

The oral drug it seems to be extremely good as was presented in the past.

It's almost equivalent to the IV so.

You know the current schedule is that a b I D dose.

So when we say 100, <unk> hundred B I D.

Which is great.

Great.

Relatively close to where the what the.

The IV dose given twice a week was.

And the endometrial patient. This of course is five days a week.

You know three weeks out for sure.

We're very excited about the current enrollment.

Okay and May I also ask on you sounded as if you were quite confident that the yes. The dosing cohort would be enough information for you to have in our P. T. D proceed to phase two did I hear that correctly.

Well that's helpful articles written at this time.

So those are the those are the.

Predetermined level.

The levels that we have in the protocol.

So in theory. When these are done we will then we will then go to the opt in phase two.

Hum.

Of course before that that decision is fully finalized when we see the PK.

Get all of that information together, but.

We're pretty close.

Okay. So then oh.

What's my next question here.

I suppose you're not happy with the fifth dose level can you proceed to higher doses in phase one.

Yeah, because I was writing amendment, if one needs one.

Okay.

You would find that to be an unexpected thing.

And you know we don't you don't think you'll be doing that.

It's not it's not unexpected we were 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.

I've been turning out.

Okay. Thank you very much guys.

So one thing I could add Jonathan to Mark's answer is that the way. The protocol written remember we're dosing three weeks out of four weeks of the cycle.

So if we're happy with the safety of that currently.

Dosing level four we could always go to four out of four.

Weeks of treatment, which means that we're going to give it a without the break that's probably more likely than going up and the reason why this is the history of this class of transcriptional CDK inhibitors that experience diminishing returns after a certain point of exposure what threshold otherwise more drug is not necessarily better it could be worse. So for this one.

And we're more likely to go to a longer schedule that to go up in dose, but that I hope gives you a bit more color on our thinking.

Definitely U R E and lastly, you guys made a very brief.

Comment about talks on can you talk any more about toxicity, particularly up to 7500, B I D doses.

Sure we have data on the first nine so Mark These gave Jonathan your view on kind of the observed safety image of the drug.

So you know the determinant of safety in a phase one trial like this is the.

The rapidity, which you can go from there. So we have not had to expand the dose level.

So.

So far there is no there's been no drug related toxicities.

Significant slowdown.

The escalation.

The dose level.

Okay. Thank you very much.

Thank you Jonathan.

And once again, if you would like to ask a question. Please press star and one on your Touchtone phone will go down too Kumar Raj out with Brookline. Your line is open.

Hi, Thanks for taking my questions and congratulations on the progress.

With regard to the phase two and the different combinations.

How are you thinking about dosing data with regard to our safety and efficacy.

That market would you take that for hydro cleans regarding combinations.

Sure I mean.

No.

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.

Very extensive set of possibilities that we may have as.

As I mentioned before we are doing preclinical data to set ourselves up for some of these things.

Obvious ones are in today.

You know.

Discovery environment, but.

We don't have there's no specific plans to launch anything until we have our phase two dose in place.

What's the real determinant.

We can go after that.

Okay.

One more thing if I may Kumar two marks for fly, which is that we have preclinical data, suggesting that a hard recycle them and possibly other CDK to nine inhibitors could potentially they synergize preclinical with immuno oncology drugs like anti PD, one anti PD L. One.

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 with no need to go to the S. T E arby's to get approval and then propose appropriate combinations in light of the available single agent data.

This gives you a little bit more color on our thinking.

Okay.

With regard to the leukemia study it looks like the enrollment is comparatively slower compared to the solid tumor is it just the fact that after now but I'll say it see how onboarding loading part of these studies what are the factors driving the comparatively slower enrollment.

That's exactly correct, we've only opened a city the hope at this point.

M D. Anderson is only now coming on stream. So your estimate is correct, we expect enrollment to pick up in the second part of the year with two sites open and possibly will have additional sites joined the study depending on the progression of the escalation levels.

Thanks, so much.

Thank you Kumar.

It does appear that we have no further questions at this time I'd like to hand, the call back to Mr. <unk> for closing remarks.

Thank you operator, and thank you everyone for joining our cycle of ourselves 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, 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 fibrosis and eventually see what see 140. Thank.

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.

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