Q1 2022 Cyclacel Pharmaceuticals Inc Earnings Call

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Starsky route.

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Good afternoon, and welcome to the cyclists sell Pharmaceuticals first quarter 2022 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.

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The company will also be accepting a limited number of questions submitted via email to the address I are at cyclists sell dot com.

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Please note today's call is being recorded.

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

Good afternoon, everyone and thank you for joining today's conference call to discuss <unk> financial results and business highlights for the first quarter of 2022.

Before turning the call over to management I would.

I'd like to remind everyone that during this conference call forward looking statements made by management are intended to fall within the safe Harbor provision under the <unk>.

<unk> Securities Litigation Reform Act of $19 95, and section 21 E.

Of the Securities Exchange Act of $19 34 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 Form 10-Q. This filing is available from the SEC or our website.

<unk>.

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

This today are Spiro <unk>, 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.

Spiro will begin with an overview of our business strategy and progress on cyclical its clinical programs and Paul will provide financial highlights for the first quarter of 2022, which will be followed by Q&A session. At this time I would like to turn the call over to Spiro.

Thank you Regina and thank you everyone for joining us today for our quarterly business update.

I am happy to report the significant progress we made in expanding our clinical development programs. In 2021 has continued into the first quarter of 2022.

At present enrolling patients and new clinical trials remains a headwind for many biotechnology companies.

Despite these ongoing challenges the <unk> team has executed well on this clinical development plan.

We are now dosing patients across three separate registration directed phase one slash two clinical trials with our two drug candidates <unk> and <unk>.

SaaS productivity speaks volumes to the skill and dedication of our team and the strong relationships. We continue to build with several leading cancer centers in the U S and abroad.

Importantly for our stockholders, we are on track to meet our key milestones for our two drug candidates during 2022, including initial data for offered recyclable.

Despite the broad selling pressure weighing for several weeks on Biopharma equities life science innovators with competitive assets will be rewarded when markets recover.

To this end, we estimate that we have sufficient resources to fund planned operations through mid 2023 and are well placed to deliver initial clinical data highlighting our competitive leadership position.

Let us update you on our progress in our CDK <unk> inhibitor program with HUD recycling or <unk> for short.

We continue to enroll patients into phase <unk> II studies with oral <unk>.

The most advanced of these studies post six five dash 101 is evaluating <unk> in patients with advanced solid tumors and lymphomas.

Since our last update the study has reached dose level five or D. L. Five with 13 patients treated.

Dose escalation stage.

Pharmacokinetic analysis from the first three deals have shown dose proportional exposure with more data coming through in real time.

We are pleased to report that <unk> has been well tolerated and no dose limiting toxicities or <unk> have been observed thus far.

As provided in the protocol. The study has escalated to dose level five with patients dosed continuously that is daily dosing for Monday through Friday, each week in the entire four week treatment cycle.

Following completion of enrollment of five the last one specified in the protocol, we will review safety activity pharmacokinetic and Pharmacodynamic data from all phase, one patients and determine whether appropriate exposure over.

Threshold has been observed.

In addition, we will determine pharmacogenomic profiles of enrolled patients and analyze correlative data regarding protein levels.

The totality of data will help us determine the recommended phase II dose or RFP to D for <unk> in patients with solid tumors and lymphomas.

We anticipate completing this analysis in the coming weeks.

And remain on track to initiate the phase II part of the <unk> 101 study in the second half of 2022.

In our second Phase <unk> study <unk> five dash, one or two <unk> is being evaluated in patients with advanced leukemias.

Both city of hope and MD Anderson Cancer Center are open and enrolling patients with <unk> now fully recruited.

We are evaluating safety and PK in this study in parallel with findings in the solid tumor program.

As patients with blood cancers can often tolerate higher treatment levels. This study may determine a different <unk> than our six five dash 101.

As a reminder, our six five dash, one or two will explore single agent activity and also combinations of oral <unk> was approved therapies for various hematological malignancies, including <unk>.

This strategy is supported by recently published preclinical data by researchers from MD Anderson Cancer Center.

They confirmed that further site lib inhibited CDK nine mediated transcription.

And reduced levels of Mcl, one in primary cell lines of chronic lymphocytic leukemia or CLO, both as a single agent and in combination with vanilla blocks.

Single agent Phaedra showed activity across all primary CLO cell lines.

The combination of our recycling bin vanilla clocks was highly effective against CML aligns with the difficult to treat 17 P chromosomal deletion, whereas each drug alone was not effective.

As a highly selective inhibitor of both CDK too and CDK nine five drug can help restore apoptosis in cancer cell in two important ways.

By targeting CDK nine fibrous suppresses the expression levels of anti apoptotic proteins, such as Mcl one in MC.

By targeting CDK to federal jams, a cancer escape mechanism, one CDK <unk> inhibitors.

Targeting CDK to also suppresses cyclin E a cancer protein to which tumor cells become addicted.

Dosing drugs with an up up doses, enabling mechanism is thought to require continuous daily dosing.

Applying constant pressure to anti apoptotic proteins like Mcl, one Mick or Bcl two is required to prevent the recovery and regrowth of tumors.

Continuous daily treatment is how we dose oral vanilla clarks, the only FDA approved medicine in this class of anti cancer Therapeutics.

We believe that oral <unk> safety profile with a continuous daily schedule is an important competitive advantage, which has not been matched by other competitors in the transcriptional CDK inhibitor field.

Let us now turn to our oral <unk>, one inhibitor <unk> 40 or 144 short.

We designed 140 to have distinct biological and structural properties that can leverage its apoptosis, enabling mechanism.

We believe that these characteristics in addition to high potency.

And promising anti cancer activity in multiple preclinical models of some tumors and leukemia suggest a differentiated biological mechanism to other <unk> inhibitors currently in development.

Consequently, our clinical development plan for 140 will initially explore its potential for single agent activity across a range of solid tumor types and hematological malignancies.

In April we announced that the first patient was dosed in the 140 Dash 101.

Our phase <unk> II trial of <unk> as a single agent.

The treatment of solid tumors and lymphomas.

We're also pleased to have opened city of hope and MD Anderson Cancer Center is the initial sites for the 140 Dash 101 study and both have enrolled patients in <unk> one.

Similarly, with our fiber strategy one <unk> hundred one is a registration directed trial with a streamlined design beginning with three plus three dose escalation to determine safety and <unk>.

Once <unk> has been established that trial will immediately enter into proof of concept cohort stage using a Simon two stage design.

In this phase two stage 140 will be administered to patients in up to seven mechanistically relevant cohorts.

Including patients with bladder.

Breast.

Liver and biliary tract.

<unk>.

Colorectal, including <unk> Newton cancer and lymphomas.

In addition in a basket cohort will enroll patients with biomarkers relevant to the drug's mechanism.

We will provide updates as the phase one dose escalation progresses with initial data expected in the first half of 2023.

Having reviewed our clinical progress and the status of our programs I will turn the call over to Paul to review our financials.

Thank you Spiro.

As of March 31, 2022, cash and cash equivalents totaled $29 6 million.

Compared to $36 6 million as of December 31, 2021.

Following receipt after the quarter end of $3 6 million of United Kingdom Research and development tax credits.

And $1 3 million and royalty receipts.

Pro forma March 31, 2022, cash and cash equivalents of $34 5 million.

The company estimates that its available cash will fund currently planned programs through June 2023.

Research and development or R&D expenses were $5 million for the three months ended March 31, 2022, as compared to $2 6 million for the same period in 2021.

R&D expenses relating to fund recycling with $3 6 million for the three months ended March 31, 2022, as compared to $1 7 million for the same period in 2021.

Due to increase in clinical trial costs associated with the ongoing clinical trials evaluating Farnborough in phase one two studies along with an increase in non clinical expenditure.

Additionally, R&D expenses related to <unk> $141 1 million for the quarter ended March 31, 2020, as compared to $1 7 million for the same period in 2021.

Due to costs associated with the opening of clinical trial sites and the start of the phase one two study evaluating <unk> 140 in solid tumors and lymphomas.

General and administrative expenses for the three months ended March 31, 2020 to a $1 6 million compared to $1 7 million in the same period with the previous year.

A decrease in professional and recruitment costs.

Total other income net.

For the quarter ended March 31, 2022 was $1 3 million compared to <unk> 1 million for the same period of the previous year.

The increase of $1 2 million for the three months ended March 31 2022.

It's primarily related to royalty income received from Thermo Fisher scientific.

United Kingdom Research and development tax credits were $1 1 million for the <unk>.

Three months ended March 31 2022.

As compared to <unk> 7 million for the same period in 2021.

The direct consequence of increased qualifying R&D expenditure.

Tax credit receipts of $3 6 million in respect of the financial year ended December 31, 2021 were received in May 2022.

Net loss for the three months ended March 31, 2022 was $4 1 million compared to $3 5 million for the same period in 2021.

Operator, we are now ready to take questions.

At this time, if you would like to ask a question. Please press star one now on your telephone keypad withdraw yourself from the queue. You May press the pound key again to ask a question press Star one now on your Touchtone phone.

We will take our first question from Kevin <unk> of Oppenheimer <unk> company.

Okay, great. Thanks for taking our questions.

Yes, congrats on a lot of solid progress in terms of enrollment, yes, Farah with regard to RF Andre.

I guess two questions.

Yes first of any patient has been dosed in cohort five comp.

A comment with regard to no DLT as of today and I just want to appreciate that includes any exposures at cohort size.

Sure Kevin. Thank you for your question, Mark which presents for that.

So the answer the questions.

This positive yesterday of what we have.

A patient who is almost done with the short cycle is doing very well.

Great and then in terms of.

I am frame our venue to update the investment community.

On the dose escalation for oral <unk> in solid tumors.

It's still reasonable to expect an update in the summer timeframe or just any perspective there.

Yes, so we expect to do a company R&D events. This R&D day is probably going to happen in the summer or more likely early some of them late summer, but that of course depends on the ability of data becoming available as we mentioned in the prepared remarks. So this is imminent.

Terrific and then with regard to <unk>.

<unk> 510 to the hematologic malignancy study can you just remind us.

Kind of where the starting doses there relative to the exposures, we have seen in solid tumors and kind of.

Thought process on how one might think about.

Yes.

The pace of <unk>.

This escalation, particularly in light of there being experienced.

IV far driver in this population.

And so there's also a question for Mark if you could please answer the.

Question on the strategy behind the heme dosing.

Yes, so essentially is identical to the volatility of dosing and just a question of <unk>.

Which one would start first.

And of course, the solid tumor trial has told.

Lay ahead.

And we're taking steps now to bring the.

Give me a trial in line with the doses that we have in the solid tumor trial. So.

There is a gap, but it will be close very shortly.

That's great.

I guess I will get back into queue and ask any questions. Thank you.

Thank you.

Our next question comes from AHU Demir of Lindenberg Thalmann.

Hello. Thank you for taking my question congratulations on the progress this is impressive.

I'm going to ask about.

<unk> already programmed my first question will be how many anticipate do you have and how many additional sites do you plan to open and following up on that question would be if you could elaborate on the dosing schedule, but I know, it's a little bit different than other peer attaining inhibitor just curious.

On the dosing schedule as well.

I'll take the first part of your question and thank you for that and Mark will answer the second question about the dosing strategy. So we've opened the same two sites for this drug as well for 140 Dash 101 based on strong interest in the mechanism, but there's a large number of centers behind which we may not open right.

The reason is that this is a new program.

Now about less information about the drug IV, then with your with far drop and will need to move carefully but also and very strategically we have strong reasons to believe that 140 may have single agent activity.

This was the case with the earliest member of the family Atlantic cancer drugs velocity.

But that has not been thoroughly explore by other sponsors pursuing the same mechanism. So this is something that we'd like to do very carefully and very thoughtfully before we got off to a wide number of sites identify both PK and PD profile as well as look for requirements. So thats one of the reasons why Glenn with two initial centers is probably the best strategy.

Now I'll ask mark to discuss the dosing.

Hi.

Sure.

As Joe said correctly, we're very interested in.

During the simulation.

This.

Doug.

So.

<unk>.

We have an oral drug.

Which we believe for our studies is well tolerated.

Yes.

<unk>.

Maximize the potential of our oral drug and to give you as frequently as tolerated.

Following the PK and the mechanism of action and.

So I guess the goal being tried giving us continuously as possible.

Tolerated, but as we're just getting started and it's hard to predict.

That's our plan.

Just to give some more color to our whose question on starting dose.

Single digit milligram range. This is a very important drug possibly the most potent drug we ever made at Cyclostyle in our history.

Which means that we will escalate in slow steps.

If you compare our agents with one answer to it but the other clinical candidate in this space you would note that they have almost identical of ICI <unk> potency against <unk>, one and very similar sort of your ability.

Which means that we're not going to be very far away from the flat dosing that they have seen in their studies of course, we need to escalate in our program and identify as Mark said all of the other information we need.

We feel very comfortable this is the right dosing strategy.

Thank you Spiro.

Remarks, you had made but differentiation differentiating profile.

140, compared to other PRT, one inhibitor could you elaborate on that what are the differentiating factors.

Sure. Thank you for that I would say that in the context of velocity with the earliest drug in this class.

140 has more in common.

Including the potential to show single agent activity, which was reported with velocity some years ago.

The main issue with velocity, which is differentiated in the 140 profile is IV dosing and long half life.

Almost three days or 100 hours plus in the case of 140 drugs given orally as Mark explained and we have a very short half life, possibly best in class around 11 hours.

The second driver of the class on Vansittart has 24 hours of half life. It is given orally is seems to be well tolerated. However, it has not been tested as a single agent the sponsor one straight into combinations almost from the beginning of the clinical development plan.

It may be appropriate for the drug and we feel that based on its differentiated biological mechanism on 40 deserves an evaluation as a single agent who will be able to show at our R&D event. Some additional preclinical data some of which is produced by investigators who we hope will join our study which would document that on.

Top of company owned data. So we have strong preclinical fact base to believe that single agent activity is feasible and we tend to pursue this in the clinic.

I have one last question again on the 140 program looking actually indication selection what is the rationale behind choosing such different indications bladder CNBC what was the rationale behind it.

Sure Mark would you like to answer his question. Please.

Well. Thank you every one of the targets that we've identified as the cohorts.

What you see.

Okay, one related mechanism.

So.

Does either data that we have from investigators.

Preclinical work.

Work that was done with.

With with previous.

Hey, Jason with glass or published data on <unk> one.

Second as an independent.

Independents.

There are all these are all all of these targets were.

With the.

Our group of investigators and we believe they are all potential single agent registration strategies, if we should see groups efficiency adequate responses.

Thank you I appreciate you taking my questions.

Yes. Thank you.

And once again to ask a question that is star one now on your telephone keypad will move next to Kumar, Russia of Brookline capital.

Hi, I'm <unk> Kumar.

The update I just had one question with regards to the CIC one program.

Different cancer tissue types for different levels of expression, which we called for a change in PD one expression.

So do you have the potential for that sort of different cancers.

Carl.

We didn't match the specified biomarkers.

Our new levels of expression.

Okay.

Mark would you like to answer this question. Please.

[laughter].

I think the good news.

Best answer will be that.

The trial is designed to answer that question. So we have a lot of we have a lot of science.

Built in.

To the study.

Specifically to answer that question, but I don't think at this point in time, there is a known threshold drove a question of sensitivity.

<unk>.

But as I say, we have a large amount of correlative studies both into built into the study.

Well, Joe as before and after treatment.

Should help clarify this issue.

Okay. Thank you just one more follow up question.

Hello.

So you have different.

Tissue types and across do you expect.

Most of that in one case versus the other or do you have what is the expectation going into the cloud.

Thank you.

Mark so.

Sure.

One of the.

What are the major pluses of the trial design that we have with the bio statistical design and the cohorts that we have the flexibility.

<unk>.

To specifically target.

Last question so.

We think there are another a number of.

A number of possible tumor types that may respond and wed like to not miss them.

So we have the cohorts that we define as well as a basket. It's data coming forward that suggests that this to another tumor that we haven't recognized may have overexpression of <unk> in this rapidly moving scientific field.

The trial has the flexibility to.

Take us into the basket and then treat them and then open them as independent cohort in each of these cohorts is a futility.

Designed to it.

If we treat X number of patients and we don't see a response that cohort will close.

No.

It's a nice way to be able to.

Treat a large.

Number of different tumor types and identify which are the best ones that will be most likely to respond with the minimal cost because it's all group into one big study.

Thank you I hope that answers your.

Question.

It does it does thank you so much. Thank you I'll get back in line. Thank you so much for taking my question.

Youre welcome.

And once again that is star one on your telephone keypad.

Move next to Jonathan Aschoff of Roth capital.

Hi, guys I joined a bit late I was wondering if this was already covered is there any point at which you rethink.

The liquid tumor trial.

Rowling since November and still in that first dose cohort I was just curious if you've kind of had.

Time by which you might rethink doing that at all.

That's an excellent question of course, given the stock market pressures that we discussed earlier this could be an opportune time to give it some attention. However, we do believe that <unk> is particularly well suited to this mechanism considered for example that the standard of care in the United States.

Was the network blocks with Apple Macs, letting agents is associated with treatment failure. When mcl one levels go up this is almost too good to be missed an opportunity to test. The CDK inhibitor. The delay you mentioned was primarily due to logistics it took us longer to open one of the two sites. We have in this study primarily because.

Of process and the year end issues now that both sides are open we expect to expand it to more rapidly.

I also made the remark earlier regarding the fact that we can analyze safety data from the solid tumor study and hopefully interpolate that into the leukemia program is.

As we all know patients with leukemia, and sometimes tolerate higher doses of anti cancer therapies. So this is a program that will at some point.

Bifurcate, possibly diverged from the solid tumor recommended phase II determination. So that's one of the reasons why this whole thing of this program now would not be appropriate, but certainly it's something we will consider in totality of data once we get across one or two more dose levels. So we're not far away we will soon.

I have an answer whether this drug is suited for patients with Hematological malignancies Jonathan.

That's good to hear thank you Spiro.

Yeah.

Do you have any other question for us Jonathan.

I guess now so operator, we can take the next question. Please.

Once again that is star one to ask a question one moment, while we queue.

And it appears that we have no further questions via the phone lines I'd be happy to return the call to Mr. <unk> for any closing remarks.

Thank you Leo and thank you everyone for joining sacked myself first quarter earnings call.

As mentioned earlier <unk> is poised to enter an important period and we expect key pipeline Readouts, which may be transformative for the company.

We believe that all of our recycling and see what C 140, or two differentiated clinical assets with strong potential for activity across multiple types of cancers, and first or second in their respective classes.

We look forward to providing additional updates and initial clinical data in the next quarters. Thank you.

This does conclude the cyclists sell pharmaceuticals first quarter 2022 results conference call and webcast. You may now disconnect everyone have a great day.

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