Q4 2020 Cyclacel Pharmaceuticals Inc Earnings Call
Ladies and gentlemen, this is the operator today's conference is scheduled to begin momentarily until that time your lines will again be placed on music hold thank you for your patience.
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Good afternoon, and welcome to the cycle sell pharmaceuticals fourth quarter and full year 2020 results conference call and webcast.
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Please note today's call is being recorded.
And I'd like to turn the conference over to the company.
Yeah.
Good afternoon, everyone. This is Jason Assad and want to thank.
And for joining today's conference call to discuss cycle sales financial results and business highlights for the fourth quarter and full ending full year ending December 31, 2000, and 'twenty before turning the call over to management I'd like to remind everyone that during this conference call forward looking statements made by management are into.
Tended to fall within the Safe Harbor provisions of the private Securities Litigation Reform Act of 1995 and section 20 <unk> of the Securities Exchange Act.
1934 as amended.
Set forth in our press release and forward looking statements involve risks and uncertainties and may affect the company's business and prospects, including those discussed in our filings with the SEC.
Among other things our forms 10-Q and 10-K. These filings are available from the SEC's website, all of our projections and other forward looking statements represent our judgment as of today and it's like a cell does not take any responsibility to update such information with us today are Spiro robotics, President and chief.
Executive Officer, Paul Mclaren 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 accomplishments on cycle sales clinical programs and Paul will provide financial highlights for the fourth quarter of 2020, which will be <unk>.
Followed by Q&A session at this time I'd like to now turn the call over to Spiro.
Thank you, Jason and thank you everyone for joining us today for our fourth quarter and full year, 'twenty and 'twenty business update call.
On our last call. We introduced you to Dr. Mark Kirshbaum, our recently appointed Chief Medical Officer.
After reviewing our pipeline Mark has made these recommendations regarding the composition of our team and clinical development plans.
On today's call will provide an overview of the clinical development strategy for fiber cyclic and see what see one and 40, which was designed to deliver registration directed outcomes for multiple indications.
Based on the mechanism of action of recycling and see what see one and 40, we have decided to advance the next stage of development for both drugs as oral agents.
Based on preclinical and clinical data collected to date supporting and the optimal biological dose.
Continuous pressure on their respective targets requires daily dosing.
This is best achieved by the oral route.
And so what patients and doctors demand during and after the global pandemic.
Let us first review the plan for fiber cyclic or fodder for short our CDK tourists last night and inhibitor.
Cadre is differentiated by its unique targeting of both CDK too and city canine.
Inhibiting CDK to results and reduction of Cyclin E and.
And city canine and reduced expression of Mcl, one and Mick and other short lived transcripts.
Elevated levels of these proteins correlate with the development of cancer resistance and jamming of the Antiapoptotic mechanism by which a healthy body controls proliferation of cells.
Our strategy with far draw is to suppress this proteins pharmacologically and and reactivate the antiapoptotic machinery, leading to cancer cell death.
Yeah.
Given intravenously Farnborough has demonstrated in patients durable suppression of mcl, one and another mechanistically related proteins, including cyclin E and Mick and tolerated doses.
Anti cancer activity, including durable partial response as a mono therapy was observed in heavily pretreated patients with solid tumors, nearly all of whom had amplification of mcl, one second E and our mix at baseline.
We believe these findings make draw a leader in the race to bring to market medicines that work on this cancer pathway.
And as reported at the 32nd EUR T C and C I ACR symposium last quarter.
And the patient with Mcl, one amplified endometrial cancer, who had achieved radiographically confirmed PR. After four cycles is continuing treatment for more than 18 months with reduction and her target tumor lesions having reached 96%.
We also reported pharmacokinetic and Pharmacodynamic results and high bio equivalents in five patients treated orally compared to patients treated intravenously on the same schedule.
Yeah.
And our Hematological malignancies program, we're evaluating far draw and combination with vanilla plaques in relapsed or refractory CLO and AML.
Anti leukemic activity consistent with the mechanism of action and good Tolerability was observed.
In the C and I'll study three patients achieved <unk> negativity, well and the combination one and bone marrow and two in bone marrow and peripheral blood.
The latter two patients also demonstrated continued shrinkage of lymph nodes why I love the combination.
In AML anti leukemic activity was observed in four out of 12 patients treated with escalating doses.
Our clinical development plan for five draw includes a streamlined phase one and busy slashed II clinical study in patients with advanced solid tumors to start and the first half of 2021.
The study design includes a phase one and be part.
With patients receiving continuous escalating doses of oral <unk>.
European.
The phase II part includes five patient cohorts defined by histology, including breast and.
And Dmitry O and ovarian cancers.
And our sixth cohort is designated as a basket, which could include additional histology and enriched for pharmacodynamic markers or relevance to five drugs mechanism.
The study design allows rapid expansion or discontinuation of a cohort subject to observation of efficacy signals based on Prespecified statistical rules.
Phase two expansion cohort outcomes are designed as a registration directed which is predicated on discussions with regulators is a strong efficacy signal is observed.
The design also includes the possibility of combination treatment and relevant histology as is required by available or emerging standard of care.
We believe this streamline design represents and efficient use of patient and capital and resources.
And increases the probability of success.
Multiple tumor types.
We will disclose further details as the study gets underway.
We are designing a similar second protocol with oral far draw for patients with Hematological malignancies.
This phase <unk>. Two study will include four leukemia cohorts and the fifth basket cohort.
Let us now turn to the anti mitotic program and the plan for see what see one and 40, our polo like kinase or <unk>, one inhibitor or 144 short.
It's like far draw was discovered in house.
140 is a small molecule high potency BLK, one inhibitor, which has demonstrated potent and selective target inhibition and impressive efficacy and cures and human tumor and leukemia, Zeno grafts and non toxic doses.
We believe that one and 40 is differentiated by P. L K family selectivity.
Administration by both the intravenous and oral routes.
And a short half life.
BLK one is essential for dividing cells.
However, normal cells with impact sales cycle checkpoints are less sensitive to <unk> depletion.
A short half life, therefore enables dosing flexibility and patients and may minimize potential effects on non malignant hematopoietic cells.
BLK won over expressing tumors with levels correlating with patient prognosis.
Answers, such as esophageal and gastric leukemia, non small cell lung cancer, ovarian and squamous cell skin cancers, as well as make 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.
Seven patients with advanced leukemias and have been recruited so far to our first in human and single agent dose escalation study or 140 given intravenously.
No dose limiting toxicities have been observed thus far.
Encouragingly the last patient enrolled on the third dose level with a proliferative form of leukemia experienced reduction in leukemia blasts, both and bone marrow and peripheral blood.
Like <unk>, we believe the optimal biological doses can be achieved by oral administration 140.
Our clinical development plan for 140 includes a third streamlined phase one slash two clinical study in patients with advanced solid tumors to start and the second half of 2021.
Which is largely similar to the federal program.
The phase one part would enroll patients receiving continuous escalating dosing of oral one and 40 as a monotherapy.
The phase II part includes five patient cohorts defined by histology and the sixth cohort designated as a basket and enriched for PD markers of relevance to enforce these mechanism.
Like far drop we also plan to open a fourth phase once last two study in leukemia with oral <unk> hundred 40.
Let us now provide brief updates on the investigator sponsored trials over I S. T S.
We are collaborating with and international cooperative group to evaluate far draw and pediatric cancers, including high risk neuroblastoma and aggressive cancer, often associated with MC amplification and pediatric leukemias.
We will provide updates once we're informed that this study has opened for enrollment.
Our first generation of CDK to slashed nine inhibitor Sally cyclic is being tested and a phase two multi center open label I S. T sponsored by Cedars Sinai Medical Center.
Evaluating safety and efficacy in patients with Cushings disease.
Reduction of mean urinary free cortisol 24 hours. After the last administration was observed in all eight patients enrolled.
However, non met the primary endpoint of urinary free cortisol less or equal to the upper limit of normal.
Or above upper limit of normal, but more than 50% lower than baseline.
The investing gives his report the preliminary data are encouraging.
Sales cycle. It was found to be generally tolerable and we'll continue enrolling patients.
This study is funded by the Fda's office of orphan products development through 2023.
And third I S. T is sponsored by the Dana Farber Cancer Institute.
And is evaluating a combination of sub instead of being with a lot per rep.
Astrazeneca has been pars, though in patients with BRCA mutant breast cancer.
Seven patients have been enrolled to date with two partial responses and prolonged stable disease observed.
Lastly, let us provide and update on our preclinical collaboration with the MRC Center for inflammation research at the University of Edinburgh, comparing far draw to Sally cyclic as a potential treatment for COVID-19 and pneumonia.
Cute lung injury or acute respiratory distress syndrome.
The study was based on extensive research carried out and professor Adriano Ross's laboratory, which demonstrated that mcl, one downregulation by Sally cyclic induced anti inflammatory effects and.
And promoted resolution of inflammation and relevant models.
Initial results from the comparative program confirm the hypothesis that fall draw is active in this setting than southern cyclic and in line with its higher dose potency.
The investigators consider that further clinical and potentially clinical research is merited to prove the therapeutic use of far draw in COVID-19, and pneumonia and other pulmonary diseases.
During the year, we continue to move our programs forward to multiple data outcomes over the next two years.
Our upcoming key milestones include.
First patient dosed with oral for recycling in phase one being lost to advanced solid tumor study.
The first patient dosed with Oracle and see what see one and 40 in phase one two advanced solid tumor study.
Manufacturer clinical supplies of Fibrocyte glib, and see what see 140 for registration enabling studies.
Data on safety and anti leukemic activity from the IV for recycling and vanilla clocks phase one study in relapsed or refractory AML and CLO.
Data from this up a citizen and vanilla clocks phase once last two study in relapsed or refractory AML or Mds.
Initial data from the C. What's the one and 40 phase one first and human study in patients with advanced leukemias.
Data from the Phase one base last two I S. T. A subsidiary being elaborated combination in patients with BRCA mutant metastatic breast cancer when reported by the investigators.
With capital on hand estimated from early 2023, we have the resources to deliver key milestones in our clinical programs.
I would now like to turn the call over to Paul to review, our fourth quarter and full year, 'twenty and 'twenty financials Paul.
Thank you Sir.
As of December 31, 2020, cash and cash equivalents totaled $33 4 million compared to $11 9 million as of December 31st 2019.
The increase of 20, $21 5 million was primarily due to $29 5 million of net cash provided by financing activities.
Net by net cash used in operating activities of $7 9 million and $1 million of net cash used in investing activities.
Research and development expenses were $1 4 million and $4 8 million for the three months and year ended December 31 2020.
And as compared to $1 4 million and $4 7 million from the same period in 2019.
R&D expenses relating to the transcriptional regulation or CDK inhibitor program with that recycling and.
Increased $5 5 million from.
$3 $1 million per the year ended December 31, 2019 to $3 6 million per the year ended December 30.
At December 30 <unk>.
2020.
And so clinical evaluation of counter cyclic progressed.
R&D expenses relating to C Y C 140, <unk> decreased by $1 1 million from <unk> 7 million from the year ended December 31, $2019 6 million from a year ended December 31st 2020.
Primarily as a result of reduction and expenditures associated with drug supply and manufacturing, which were not required in 2020.
Other R&D expenses decreased by $1 million.
From <unk> 4 million per the year ended December 31st 2019 day.
And $3 million per year ended December 31, 2020, due to a reduction and consultancy costs.
General and administrative expenses from the three months and year ended December 31, $2021 7 million and $5 9 million, respectively, compared to $1 4 million and 5 million per the same periods of the previous year.
Total other income net for the three months and year ended December 31, 2020 were $14000 of expense and $1 million of income.
Compared to 41006 million free income from the same periods of the previous year.
The increase of <unk> 4 million for the year ended December 31, 2020 is primarily related to income received and an asset purchase agreement with them and Fisher scientific.
The United Kingdom, R&D tax credits were <unk> 4 million and $1 2 million for three months and year ended December 31st 2020.
As compared to <unk> 3 million and $1 3 million from the same periods and 2019.
Our net loss for the three months and year ended December 31, 2020 was $2 8 million and $8 4 million.
Compared to $2 5 million and $7 8 million from the same periods and 2019.
The company raised net proceeds of approximately $29 7 million during 2020 from agreements to sell securities and warrant conversions.
And additional $4 $3 million and proceeds from warrant conversion.
<unk> received following the year and.
The company estimates that the pro forma cash resources of $37 7 million, which includes proceeds from recent warrant exercises. After December 31 2020.
We will fund our currently planned programs through early 2023.
Operator, we are now ready to take questions.
Thank you as a reminder, ladies and gentlemen, if you wish to ask a question simply press Star then the number one on your telephone keypad again that is star one.
Our first question comes from the line of Jonathan Aschoff of Roth Capital Partners.
Hi, guys.
And thanks regarding P. L. K, one and condition why is the field generating so much interest from investors and drug developers after having been dormant for so long and what's changed.
Jonathan and thank you very much for your question, it's really hard to say why do you feel has become a hot again, but of course clinical data usually the reason and as we mentioned and our remarks.
And the other compounds into clinical development has recently shown activity and a single arm study and.
And metastatic colorectal cancer that was K Ras mutated and we all know chaos is one of the Holy Grails and modern oncology drug development and thought to be Undruggable until recently.
The activity of the P. Okay, and one drug from the competing company was broad based encompassing several mutations and that suggest broad therapeutic effect.
Believe that C. What's the one and 40 may have similar activity based on preclinical data.
Thank you Spiro one more is that regarding CDK to nine you know versus to what day to support one approach versus the other given that both approaches like vanilla clocks and a legitimate and.
Anti apoptotic.
Okay.
Well, that's a great question because of course, vanilla clacks inhibits the bcl two protein, which is known to be and anti apoptosis marker.
There are however, many other proteins that are members of the same D. C O two family and they include Mcl, one which is targeted by hydro. It also includes B F. L. One.
D C L W and Bcl XL and all of these proteins work in tandem they both have a short life called therefore, shortly and transcripts. So I suppose that any CDK and nine inhibitor could potentially work and these mechanisms that should be able to transcriptional really modulate the expression or.
<unk> of these proteins, where the desired effect of activating apoptosis and it's hard to see and Mcl, one only targeting from pound work as comprehensively because of course inhibiting mcl one itself may be compensated by other proteins that can be up regulated at the same time.
And lastly, what about CDK too.
We believe that <unk> is the only drug that hits, both cdk's, two and CDK nine.
And as reported and non clinical data these protein.
And as happened sometimes at the same time and the same patient. So several of the patients that had tumor shrinkage on fad per single agent therapy had simultaneous amplification of mcl, one and cycling knee.
And drug that doesn't hit syndicated too is probably not going to have a lot of activity again cycling the amplified tumors and in this regard and CDK to nine drug like fanta with enjoy some broader activity profile and possibly address and larger commercial market opportunity.
Spiro and thank you Keith and I have one one with Paul just briefly in the fourth quarter and ease of R&D and G&A numbers kind of a spike or a day a trend going forward.
And Jonathan I think the they are a trend.
As you heard in the remarks pay we're looking to start a clinical study with Farnborough and 140 in 'twenty and 'twenty, one and should we expect that the Q3 to Q4 trend would continue on the R&D and G&A, we expect to be flat relatively flat from the Q4 going forward.
Okay. Thank you very much guys.
Thank you.
Our next question comes from the line of Kumar, Russia of Brookline capital markets.
Thanks for taking my questions.
First with regard to half life false Cys, one part B, how does it compare with what sort of day.
And also in terms of the patients that have been dosed with the in probably and as dosing.
How does that compare in terms of efficacy is seen in the animal models.
Yeah.
Okay. Let me take the second question first and I'll ask Dr Kirshbaum, and Mark to pick up the first question pre clinically we've seen curative effect or see what see 140 and virtually all of the King air models tested cause or leukemias grafts.
And the tumor gross lines simply flatline. They go down to zero up on application of see what she went and 40 is probably the most potent drug we ever made and there.
And we came up with clinical and see no grafts.
So we are happy to see the first indication of activity as we mentioned in our remarks with a patient with a third dose level, we're showing blast reduction after C. Hornsea, one and 41 on therapy, but let's not forget Kumar, but this is potentially a class effect given the success of a lesser too early and phase two and addressing this disease.
Setting of AML.
Mark would you mind answering to the second or the first part of the question, which is about the elimination half life or 142 versus non banks or tip.
Yeah.
The comparison and visited by it.
And speak to that here, but.
We believe that the short half life is.
Positive.
And that.
Having short half life with minimize toxicity and also allows us to maximize the potential of the drug Buddy.
And with repeated dosing switches.
Again, much more feasible with an oral drugs and and IV drug.
Okay and in terms of the orally.
Or trials.
And looking Minneapolis.
Solid two months what are your expectation in terms, how far starting those standard.
Yeah.
Mark that's a question for you as well.
Well.
And these trials will be designed with input from the FDA, so they're starting dose levels.
And as a result of the collagen and the animals etcetera.
And we'll be and compliance.
The normal procedure from that.
So will there be some overlap with regard to the intravenous like what what what data from the intravenous trials can be U D. What is being done from the order trials.
Well, we get a certain amount of PK data from the IV drug.
But much.
Much of this need will be regenerated again.
Based on the studies and are ongoing now and as we get into the as we get into the clinic.
And I also wanted to know.
Many of them.
Okay.
And also what you already are seeing some chop combination.
And especially bad.
And in fact and and even the Martin's.
I think both agents had GAAP.
Very very good capacity from combinations.
The critical thing is first to get the single agent activity.
One net well determined and we understand how the drug works as a single agent.
There is a whole host of potential combination.
Sure.
Even addressing the question that came up before and my own like academic career and publish some things of that sort of along.
Along those lines.
With that with drugs of this at this time.
So hopefully.
Some of those will be built into some of the studies and some of them will be added as we get out of a dose and you can see.
Our ideal target of activity.
And maybe finally lean Dom south and the initial data from the IV study.
And what can we expect when those present later this year.
Well, we don't know yet because the price just enroll three dose levels, but as Mark explained it is very likely that the events will be overtaken. This is a pandemic and I'm still with many parts of the country and locked down so patient enrollment.
And I'm reluctant to get IV therapy, So we suspect as we open and a few weeks.
And the five alright, and later on and see what she want afford the oral programs. If we gave a patient and the choice they will vote with their feet, particularly oracle.
And I'll give precise jacket and some time from the survey please.
And B here.
And of course there'll be a calls like this on a protest and force any activity and responses observed.
Thank you so much.
Yeah.
Thank you.
Again, ladies and gentlemen, if you wish to ask a question simply press Star then the number one on your telephone keypad.
Our next question comes from the line of legacy Lee of late and pad.
Okay.
Hi, Thanks for taking my questions.
A question.
And if I just secondly, Spiro you discussed the molecule.
And I was making is that we've got.
None and the C D E and maybe could you also.
And why the update.
And it wasn't the Lady and unique.
From north and their competitors.
And so you think and nine turkeys and the C D.
And Q targets or any other income.
Impose.
Ladies and <unk>.
And what I see.
Like the ones, we have seen very limited data and the fan.
And then see if Cindy prescription drug, which as you point out.
And it either.
And our alcohol and palms and hit only CDK and I.
And so to me the most proximal drugs was.
Following up from the clinic.
And why on fire.
And as you need.
Four of $5 73.
Both of those stores that are getting and stuff.
Oh this free game.
And sitting here too.
And we won't be and clinical data have recently published and FCC Dick.
Compound, which appears to have activity against them and intravenous drug we don't know yet about the recommended phase two dose and.
And from earlier Phase one studies it appears that they were.
Just a couple of CR and.
That market share and when they come up.
Sure.
Oh no.
The fourth from a free drugs.
Very much because there's a little bit from the clinic to connectivity and look to be.
And as expected and act and state the canine drug.
But let's talk about annuities.
That would be.
And of course.
And once that's.
And finally in terms of silver and two drugs and field there isn't it and let's see the reason for that is that some.
And some time ago to major and personal published by academic investigators and then because I just didn't want and need.
Which show that.
And otherwise.
Cynthia do the.
Okay.
Fishing and clean.
And I hope that the SaaS and think escape and go back.
And basically these are the low.
And time.
For drugs.
Thanks.
And there are lot more sleep trial.
And this will fail CDK four six inhibitors.
Have amplification of cycling me, which of course is targeting CDK to as we've seen and cycle and so clinical data with gross site.
Interest in Sydney.
She has been cancelled.
There are two drugs I wouldn't know her and her.
Phase one trials.
And our CDK four and six inhibitor.
I don't think it's sitting and waiting.
And I feel even.
And remember because as I mentioned earlier and maybe another six months.
Or was there and my I'll step out there from a file relative doses and for them.
Ability.
There appears to be some concern.
Two weeks ago, but almost a depression.
And 246 drug or simply attributable with CDK six targeting and it still.
The net sales in the courts and no clinical activity was from same.
Same store per patients. So this is an evolving work in progress.
Of the three sites.
And even sitting here too.
And balance sheet.
And then two are twofold.
Getting the neighbors.
Okay.
Got it thanks for the average age.
And then a question on the U K.
And Heath Terry.
And you mentioned the sort of hot fly earlier.
And any other color you can share regarding the molecule difference or any and you need.
Your friends.
Yes.
Deep oncology drug and.
Yeah.
Our strategy.
Certainly.
Ah report and what it's all likely non and I'll ask mark to that comment.
Zone from.
She has conducted and research.
And one investigator.
And he's going to neighborhoods.
There are pretty cool.
Yeah.
And of course, the Burger and the criminal.
Charles and the problem and same day and rent that's cheap price.
Andrew.
And if we're talking about.
And we see police and the way that claim.
Potential success.
From a rectal cancer space and there's a lot of 14th week.
Say that drug.
And last one day.
However, both on land and survey.
And hit.
Good day, one almost the same importance and level.
And in a moment.
So it's really hard to explain.
That difference.
Your friends and times off peak day P D or eventual ability from both drugs.
And given that particular target and.
Moving on.
Rob.
So at this point, we would presume that the drug and it will probably be developed from a similar path.
And as Mike explained interested in pursuing expansion activities person from dawn to combinations.
Barclays rocks and ticket and Furthermore, on a weighted this question.
Well I would just add that.
And the past.
And with structured more similar to ours.
It had single agent activity in various tumor types and we believe that our agent has an advantage over those drugs and that.
It has a showed a half life and the ideal what appears to be the ideal kinase profile.
For for this kind of activity. So we believe that we will see single agent activity.
Okay and that without with much less toxicity that was seen in the past.
With that agent.
We can replicate the single agent activity and be able to develop it.
Further.
Alright.
Last question and maybe aspect with your price.
And is there any rationale and simple.
And the combination.
Next day.
Good morning inhibitor, and New York and benign.
And your prepared remarks that question because yeah.
And he also has a.
So you need to see to get more.
So that's an excellent question.
The answers are Ron and I thought.
Program passport centralized activity level and the synergy between part a and b, Okay, and Mercedes kits and my income.
What's your interest of issue.
Meredith and cars Daily me have all packed with them right.
And it's made it it must be in Arizona.
Good day and then.
And for them and they have complementary activity.
So at the time and doing spoke up and it should take to unapproved brought it forward. So it's probably best to develop each drug as a single agent and the once activities do you find them to consider what is the appropriate covenants. So that's good.
And the case the future about from now I think we.
We expect to develop those drugs initially and simulations.
Yeah.
Okay got it makes sense.
Thanks for answering my question.
Thank you and as you think differently.
Okay.
And at this time and I'm showing no further questions I'd like to turn the floor back over to management for any additional or closing remarks.
Thank you operator and.
Thank you for participating.
Sales fourth quarter, and full year, 'twenty and 'twenty earnings call.
We appreciate and support for our efforts.
And and realize stockholder value by demonstrating safety efficacy and cost effectiveness of our medicines.
We'll look forward to updating you on our progress and some of your upcoming conferences and road.
From a person please stay safe and well and.
And right at this time and manageable.
Thank you ladies and gentlemen, this does conclude today's call you may now disconnect.
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Yes.
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Okay.
And.
Yeah.
And then.