Q1 2021 Cyclacel Pharmaceuticals Inc Earnings Call

Good afternoon, and welcome to the cycle of sound Pharmaceuticals first quarter 2021 results conference call and webcast. At this time all participants are in a listen only mode.

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Conference call over to the company.

Good afternoon, everyone and thank you for joining today's conference call to discuss cyclists sales financial results and business highlights for the first quarter ending March 31, 2021 before turning the call over to management I would like to remind everyone that during this conference call forward looking statement.

It's made by management are intended to fall within the Safe Harbor provisions of the private Securities Litigation Reform Act of $19 95, 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.

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 <unk>, President and Chief Executive Officer, Paul Nick Barron Executive Vice.

President Finance and Chief operating Officer, and Dr. Mark Kirshbaum, Senior Vice President and Chief Medical Officer.

Bureau will begin with an overview of our business strategy and accomplishments on Cyclostyle multiple clinical programs and Paul will provide financial highlights for the first quarter of 2021, which will be followed by a Q&A session.

At this time I would like to turn the call over to Spiro.

Thank you Irina and thank you everyone for joining us today for our first quarter and business update call.

On our last call in February we provided an overview of the clinical development strategy for Fahd recyclable and C Y C 140.

Our main objective remains to advance these targeted orally administered candidates into registration directed outcomes for multiple indications.

We are pleased to report that we have achieved the initial T milestone delivering on this strategy with FDA clearance or I N D. Four offered recyclable or fabra from short in a streamlined phase one b slash two clinical study in PAH.

<unk> with advanced solid tumors.

We expect to open this study in the next few weeks once contract discussions with the sites are concluded.

The study design includes a phase one b part with patients receiving continuous escalating doses of oral fabra with the objective of defining a recommended dose for phase III.

Although we will initially evaluate far draw as monotherapy. The design includes the possibility of combination treatments in relevant histology as required with available or emerging standard of care.

It is worth noting that before entering this phase one b study with the oral formulation Cyclostyle has generated a significant amount of clinical data with the IV formulation in solid tumors as a monotherapy and in liquid cancers as combination.

In addition, we presented oral bioavailability data in October 'twenty, 'twenty, which demonstrated comparable dosing characteristics between the oral and IV forms with respect to half life maximal concentration and area under the curve.

We believe theyre highly informative data generated from these earlier studies will help us determine the optimal dosing level for the oral formulation in an efficient manner.

The phase two part will include between at least five and possibly up to eight cohorts defined by histology.

These will include breast.

Colorectal, including K, Ras mutant endometrial and ovarian cancers and certain lymphomas.

An additional basket cohort will enroll patients with relevant biomarkers to the drug's mechanism, including Mcl, one Mick and cyclin E regardless of histology.

To understand the rationale for selecting these cohorts, let US review Fahd <unk> unit.

Adding feature of targeting both CDK too and city canine.

Inhibiting syndicated to results in reduction of Saxon E protein levels.

And Sidney canine and reduced expression levels of mcl, one and or Mick.

Elevated levels of these proteins correlate with development of cancer resistance and jamming of the apoptotic mechanism by which a healthy body controls abnormal cell proliferation.

Our strategy with far draw is two pharmacologically suppressed this proteins and reactivate apoptotic machinery, leading to cancer cell death.

We believe that in order to achieve optimal biological levels applying continuous pressure on their respective targets is critical.

Thus daily dosing by mouth is preferred to intermittent intravenous dosing, which may allow cancer cells to recover.

<unk> has demonstrated durable suppression of mcl, one and other mechanistically related proteins, including <unk> and MC at tolerable doses in clinical studies when dosed intravenously.

Anticancer activity, including durable partial response as monotherapy was observed in heavily pretreated patients with solid tumors.

Nearly all of whom had amplification of Mcl, one cyclin E <unk> or MC at baseline.

As an example of patients with Mcl, one amplified endometrial cancer.

Cheap radiographically confirmed PR after four cycles on single agent far draw and is continuing treatment for more than a year and a half with reduction in her target tumor lesions having reached 96%.

In further support of our cohorts selection a recent publication reported that overactive K Ras mutant cancer cells are impeded by CDK <unk> inhibition.

The authors led by Dr. Frank Mccormick of the University of California, San Francisco and the answer is Frederick National Lab for cancer Research.

Screened almost a million compounds for Ras mutant selectivity I could disrupt oncogenic Kinney Ras signaling.

They identified five groups of chemical compounds, which preferentially inhibited oncogenic K Ras mutant cell lines, including K Ras dependent colorectal cancer lines.

Three out of these five groups of active compounds, primarily inhibited CDK nine.

These findings expand on previous findings that dual CDK to nine inhibition is an optimal strategy to treat colorectal cancer.

That K Ras mutant pancreatic cancer is sensitive to CDK <unk> inhibition.

And that far dry is effective against K Ras mutant lung cancer in preclinical pdx models.

Collectively these publications support the potential for the therapeutic use so far draw in K, Ras mutated cancers, including colorectal lung and pancreatic.

In summary, our phase one b slash two strategy is informed both by the clinical activity of <unk> and the drug's mechanism.

For example, one of the cohorts will be colorectal cancer, including K Ras mutant.

Lung and pancreatic cancer patients are eligible to be enrolled in the basket cohort. If their cancers are suspected to be mechanistically related to fire draws mode of action.

The phase II study design allows for rapid expansion or discontinuation of a cohort.

Subject to observation of efficacy signals based on Prespecified Statistical rules.

Outcomes from phase two expansion cohorts are designed to be a registration enabling.

This means that if we detect a strong efficacy signal in one or more cohorts.

And confirm our path forward with regulators, we may be able to pursue an accelerated approval.

We believe this streamlined design represents an efficient use of patient and capital resources and increases the probability of success across multiple tumor types.

We will disclose further details of other cohorts as the study gets underway.

We are designing a similar protocol with oral fodder for patients with Hematological malignancies, both as monotherapy and in combinations.

The second phase one B slash two study will include several leukemia cohorts and a basket cohort.

Let us now turn to the anti mitotic program and the plan for see what Sue on 40 or 144 short on a polo like kinase or <unk> one inhibitor.

Like Fireeye 140 was discovered in house.

140 is a small molecule high potency BLK, one inhibitor, which has demos.

And selective target inhibition and impressive efficacy and cures and human tumor in leukemia is intergraph's at non toxic doses.

We believe that 140 is differentiated by P O K.

Cell activity.

Administration by both the intravenous and oral routes and a short half life.

P O K one is essential for dividing cells. However.

However, normal cells will impact sales cycle checkpoints are less sensitive to P. O K one depletion.

A short half life, therefore enables dosing flexibility in patients and many minimized potential effects on non malignant hematopoietic cells.

P O K, one over expressing tumors with levels correlating with patient prognosis on cancers, such as esophageal gastric leukemia, non small cell lung cancer, ovarian and squamous cell cancers, as well as Mick amplified cancers.

Recent data, where the only other P. L. P. One inhibitor in clinical development suggests that P. O K, one inhibition may be effective in K, Ras mutated metastatic colorectal cancer.

Like <unk>, we believe that optimal biological doses can be achieved by oral administration of 140.

We are manufacturing clinical trial supplies and are currently engaged in a N D related activities.

Our clinical development plan for 140 includes a third streamlined phase one two clinical study in patients with advanced solid tumors.

To start in the second half of 2021, which is largely is similar in design to the federal program.

The phase one part will enroll patients receiving continuous escalating doses of oral 140 as a monotherapy.

The phase II part includes several patient cohorts defined by histology and a basket cohort enriched for PD markers of relevance to 140 <unk> mechanism.

Like father, we also plan to open a fourth phase one two study in leukemia with order 140.

We will continue to move our programs forward aiming to deliver multiple data outcomes over the next two years.

Our key milestones for the rest of 2021 are.

First patients dosed with oral fabra in the phase one Beast last two advanced solid tumor study expected in the next few weeks.

First patient dosed with oral far draw in the phase one base last two leukemia study.

And the first patient dosed with oral and see what's the 140 in a phase one slash two advanced solid tumor study.

In early 2022, we plan to dose the first patient with oral see what see 140 <unk> in a phase one slash two leukemia study.

We expect to report phase one data with oral far draw in advanced solid tumors, including any efficacy signals as they arise throughout 2021.

Clinical data from the other studies will follow later on in 2022.

We will also provide updates from the ongoing phase one b slash two investigator sponsored trial of Supper center being elaborate combination in patients with BRCA mutant.

Metastatic breast cancer when reported by the investigators.

With capital on hand estimated through early 2023, we have the resources to deliver key milestones in on clinical studies.

I will now turn the call over to Paul to review, our first quarter financials Paul.

Thank you Sarah.

As of March 31, 2021, cash and cash equivalents amounted to $47 $8 million compared to $33 4 million as of December 31, 2020.

The increase of $14 4 million was primarily due to $18 million of net cash provided by financing activities offset by net cash used in operating activities of $3 6 million.

There were no revenues for each of the three months ended March 31 strength in 'twenty one.

And to 2020.

Research and development expenses were $2 6 million for the three months ended March 31, 2021, as compared to $1 1 million for the same period in 2020.

R&D expenses relating to us.

<unk> inhibitor program increased by almost point 8 million from the three months ended March 31, 2021, as we continue to progress the clinical evaluation of Phaedra.

General and administrative expenses from the three months ended March 31 2021.

The $1 7 million.

Compared to $1 3 million from the same period of the previous year.

Due to an increase in legal and professional expenses and recruitment costs relating to expansion of our clinical team.

Total other income net on the three months ended March 31, 2021 was <unk> 1 million compared to <unk> 9 million for quarter one 2020.

The decrease of <unk> 8 million for this quarter is primarily related to income received under an asset purchase agreement with Thermo Fisher Scientific Inc.

United Kingdom Research and development tax credits reported 7 million per the three months ended March 31, 2021, as compared to <unk> 3 million on the same period in 2020 as a direct consequence of increased qualifying research and develop the expenditure.

Net loss for the three months ended March 31, 2021 was $3 5 million compared to $1 2 million for the same period in 2020.

The company raised net proceeds of approximately $13 5 million from a registered direct financing in March 2021, and received an additional $4 $5 million from warrant exercises.

The company estimates that total cash resources of $47 8 million as of March 31, 2021 will fund currently planned programs through early 2023.

Operator, we're now ready to take questions.

As a reminder to ask a question you will need to press star one on your telephone.

Your question price.

Please standby.

Sure.

Your first question comes from the line of Jonathan Aschoff.

With Roth capital.

Thank you very much on I was wondering Hudson on two on also excluding the contribution of <unk>.

With me on the combo therapy.

On the trauma combo therapy whenever it is on it.

Jonathan Thank you for your question, our Alaska, Mark Kirshbaum to address that but just to remind everybody that the study is starting with monotherapy and then provides in the event that we don't see sufficient activity as a single agent to enroll combination cohorts, perhaps mark you could share your insights on that.

Our design.

Well thank.

Thank you Carol.

Essentially agree.

The trial was designed primarily.

<unk> single agent activity, we believe there are a number of.

On tumor indications, where single agent activity, they actually produce meaningful responses. So that's the primary focus of the.

Of the solid tumor trial.

Given the landscape of leukemia is that's a little different than that.

Well known drugs will be combined net of standard in leukemia world, but I think our primary goal on the cell tumor trial is.

Push for single agent activity and add combinations as we see.

Activity.

Okay cool.

All the loans.

Awesome.

What percentage of your solid from the coastal.

On a ball will halt payroll patient maybe you want some sort of cross hold on just going to take what pumps.

I think of this as again a question for Mark.

Sure.

I assume you're speaking specifically about colon cancer.

Well so so again the way. This is designed is that there is the phase one component.

Voting on this trial, which is pretty much open.

All tumor types that are relevant and then there's an individual hat on.

On a two stage design cohort.

This is really designed for colorectal cancer.

As you know.

Yes, it's a pretty significant.

Percentage of those patients.

We didn't formally exclude non chaos patient since we haven't seen yet the clinical activity overall, but.

My presumption is that the percentage of those patients will be high.

Okay. Thank you very much.

Thank you Jonathan.

Your next question is from Kevin Dede.

With Oppenheimer.

Hey, guys. Thanks for taking my questions, maybe two from me that that May have Bob as well.

With regard to the Aro <unk> study can you just comment on how youre thinking about the.

Starting dose and dose escalation given that you do have some prior exposure there with you.

What I'm really driving at areas.

How how quickly might we hope to see.

This compound move through dose escalation.

And then thanks for the update with regard to pay rise CRC.

Or.

Can you just comment on the.

The day treatment landscape for targeted agents.

Or yeah.

CRC and kind of how you see your ballpark.

On a $1 40 fitting into that landscape.

Great Let's have Mark answer your first question, Kevin about the dosing strategy based on existing IV data on it I don't think on the landscape question on chaos colorectal cancer Mark.

Thank you.

On the good news here is that based on the previous standard that we had with the IV drug we were able to model the dosing schedule based on pharmacokinetics that we already had but I can tell you that we are already in the active.

Dosing range.

From our very first dose level.

So this is we believe that we will be hitting the target already from the start.

So.

Depending on it.

Oh, how it's how well tolerated it will be increasing the number of days and then the dose, but we believe that all of our doses from the start or are within an active range.

Got it and.

I'm sorry on spare I think you actually were working on things.

The second part of that.

Yeah, you asked the question about treatment landscape for K Ras mutant colorectal cancer of course, most investors are aware that there are two drugs that are targeting a one of the many mutations characterizing the kers genotype, which is G 12 see these two drugs Socorro.

And on Digressive from.

From Amgen and Novartis, respectively have shown promising activity in non small cell lung cancer, but the data and call on the was less exciting although still promising probably would require a combination.

This has given rise to a number of new agents.

Motioning for potential combatant. Once these two drugs reached the market, but I would draw your attention to two facts first of all due to a see only addresses about 10% of the kiosk population, but at least five other mutations, possibly more responsible for treatment failure and disease progression in this cancer.

We know that the other CDK nine drugs gave on primarily intravenously.

Which means that given them to solid tumor patients who could be a challenge as we discovered with fed recyclable given intravenously as daily pressure on the target will be hard to achieve as patients even before the pandemic, especially now would be resisting daily therapy with an intravenous drug.

And finally, there is the question of what about P. O K one as we know P. O. K. One has produced P ours and a group of five patients at a 14 treated with kiosks mute on column cancer. This was as part of a triplet with the MTA Genesis agent Avastin as wireless for theory chemotherapy.

So it remains to be seen whether a P. O K one by itself as a single agent can have activity on the setting. So we intend to answer both of these questions CDK nine inhibition in our case together with CDK too as well as P. O K one inhibition as single agents in this setting of kiosk column cancer. This could be a high.

The priority for the company, but not necessarily derailing us from the already announced clinical development plan is just giving us the chance to perhaps hold on and if we see activity helped this gives you some perspective.

That's super helpful. And then my follow up thank you pertains to the dose escalation.

Escalation for the.

Oral module cycle study.

Specifically given that you're already starting at a you.

What I can tell you.

Therapeutic dose these patients.

You know on an opportunity.

You know transition to to a higher dose as you.

And to the extent that's permitted in the protocol kind of how long what.

Ah patients typically need to be able to stay on drug before having an opportunity to dose escalate.

Price Mark.

Yeah.

Any specific question about the.

About the trial function.

Don't have intra patient dose escalation built into the study at this point in time again, because we believe that all of our adjusted their active the.

The dosing schedule again is primarily increasing the number of days.

And weeks.

But.

Yeah. There is no plan for Entravision dose escalation at this point zone.

Great. Thanks for taking my questions.

Thank you, Kevin and let me say for the benefit of those of you listening by webcast that a more detail on Mark's comments is available on our presentation in the corporate presentation section of our website.

Operator back to you.

Thank you. Your next question is from.

Yeah.

Yeah.

Hi, Thanks for taking my question first.

First question on the carers.

Discovery. So you can see you have on both the CDK <unk> inhibitor in P. On it can't why aren't you better and both issuing two kind of bit of chaos.

You didn't cancer.

Do you have any insider or do you do to make them, even herbalife well it may be synergistic or.

What's the potential to combine then have any preclinical experience or it doesn't make sense to test in the trial.

That's a great question <unk>. Thank you for asking that I think there are two ways to address such a question from a portfolio management point of view it.

It seems to us that there is some biological rationale but has not been fully studied because there's a relative of recent discoveries.

As a more practical matter, though two unapproved drugs on the same protocols is a challenge from many sponsors and that's one of the reasons where people are looking to guess about the emerging standard of care and kiosks mute on colon cancer. For example, and then seek to combine it with an approved drug which we know is a tested strategy that could lead to.

Rapid FDA approval and I suspect the cycles. They will follow the same path ultimately, though until we understand the translation of our consequences of each of these drugs as single agents.

And understand what stage of.

K Ras mutational spectrum two they work is really hard to speculate on combinatorial possibilities, but it's something that I have said to me crossed our mind then we'll look at it at a later time.

Got it makes sense.

One more question on the investigator sponsored trials or some sort of being with the.

Dave.

I mean, some on them it looks quite encouraging do you have any further background on kind of on the pacing kind of based on on condition, how does it compare to the a good day.

Monotherapy trial, you know historically, if you compare this response rate and an outcome.

Outcome.

Yeah. That's a great question I think again for asking that.

Oh Wow. This question refers to the investigator sponsored trial, combining our third drug separate set of being an oral nucleoside analog with or elaborate which is the standard of care in the setting of metastatic breast cancer, which is mute on for BRCA.

In that setting there from studies called Olympiad, It's an Astrazeneca study will elaborate.

That study showed about 50% P R.

I don't believe that this is the right metric to compare this small data set as you pointed out the one Z our view is that.

Small numbers on one could easily get seduced by the attractiveness on small numbers, but we need to see a bigger population to draw conclusions. There is one point about this data, which is intriguing the elaborate and for that matter. All PARP inhibitors duration of effect is modest as we usually around a year and most per.

<unk> discontinued therapy due to more of a suppression.

We know from our studies in leukemia, the solicitor being can be taken for multiple years I believe the longest patient on surplus would've been it's been on for more than five years, which suggests that if we can stretch the therapeutic benefits with an elaborate combination in the setting of peer or durable stable disease much beyond the elaborate on single agent.

Benefit and with the create the continuum of care, which would be very exciting for this population of patients who have nothing once PARP inhibitors fail. So that I think is the main interest of the investigators who are paying for the cost of the study, but we're gonna keenly watching of course are we on frequent dialog with them as the state on false.

Got it and thanks for taking my questions.

Yeah.

Thank you Wendy.

And there are no further questions.

Okay.

Smith for closing remarks.

Thank you operator, and thank you all for participating in fact ourselves first quarter call. We appreciate your support of our efforts to deliver on our strategy and realize stockholder value by demonstrating safety efficacy and cost effectiveness of our medicines.

Please stay safe and well we look forward to updating you on our progress and meeting some of you at upcoming conferences, either virtually or hopefully in person.

Operator at this time you may end the call.

This concludes today's conference call. Thank you for participating you may now.

Connect.

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