Q3 2021 Cyclacel Pharmaceuticals Inc Earnings Call
Okay.
Good afternoon, and welcome to the cycle still Pharmaceuticals third quarter 2021 results conference call and webcast.
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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 Cyclostyle financial results and highlights for the third quarter ending September 30th 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 19.
<unk> 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 forms 10-Q and 10-K. These filings are available from the FTC 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 robotics, President and Chief Executive Officer.
Holmic Barron Executive Vice President Finance and Chief operating Officer.
And Doctor, Marc Kirshbaum, Senior Vice President and Chief Medical Officer.
Spiro will begin with an overview of our business strategy and progress on cycles, South clinical programs and Paul will provide financial highlights for the third 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 Dana and thank you everyone for joining us today for our third quarter and business update call.
I would like to begin the call by providing an update on the progress we're making across our two programs are oral CDK to nine inhibitor pod recyclable or far draw and our Oro P. O K, one inhibitor C Y C 140 or 140.
The third quarter was characterized by continued execution of our operating plan with opening of two phase one slash two studies for all Sondra and filing in I N D for a phase one slash two study all of our 140.
We have now enrolled a total of six patients across two dosing levels in our fall Rush study designated 065 Dash one O one in patients with solid tumors and lymphomas.
More recently, we announced dosing the first patient in our or six five dash one O two study or far draw in patients with leukemia.
We have also filed with the F D. A N I N D submission for an order 140 phase once last two study in patients with solid tumors.
Well, we're waiting for FDA review of the I N D. We are preparing to open. This study, which is supported by ongoing preclinical experiments supporting our choice of certain cancer histology for the proof of concept part of this study.
He has been a busy year for the company, but we are pleased to be on track to deliver as many as 15 outcomes or shots on goal from different cohorts and that too far dress studies next year.
And we are funded to deliver on these potential outcomes with cash projected through early 'twenty two 'twenty three.
Let me now review the federal program.
We are building a specialized global network of world renowned cancer treatment centers for both solid tumor and leukemia studies.
In addition, multiple preclinical collaborations are providing strong evidence in support of our choice of treatment cohorts in the proof of concept stages over there to phase one to Farnborough studies.
Both of these studies are registration directed and use a streamlined design with an initial stage to determine the recommended phase two dose or our P. Two D Oro far drop in solid tumors and separately in leukemias.
Once RFP to D has been established the studies will immediately enter into proof of concept cohort stage using a Simon two statistical rule to assess efficacy in individual cohorts.
If sufficient efficacy at tolerable doses is observed the relevant cohort will enter an expansion prior to possible presentation of the data to regulatory authorities.
In addition to seven solid tumor in 065 Dash, one O one and six leukemia cohorts in 065 dash, one or two the five studies contain a basket cohort in which patients can enroll based on the biomarkers relevant to five drugs mechanism of action.
Initial cohorts will receive five dry as a single agent with subsequent cohorts designed to treat five draw in combination with available or emerging standard of care.
In total we expect to report outcomes from 15 cohorts or 15 shots on goal eight in solid tumors and lymphoma, and seven and leukemia.
In the O six five dash one O one solid tumor in lymphoma study, we have dosed orally administered fabra to six patients in the first two dosing levels or D. Els.
Three patients were treated at the starting D. L. One level at 50 milligrams B I D for three days a week.
In D O two patients are being dosed at 50 milligrams B I D. Four five days a week.
We believe that daily dosing is important for drugs, enabling apoptosis like fabra.
Oral <unk> is well tolerated, thus far and patients are being followed up for initial assessment of efficacy.
As a reminder, durable partial response was observed with intravenously administered far draw 200 milligram two days or weeks.
We are pleased with the pace of recruitment in the O six five dash one O. One study, which is currently enrolling at city of hope and M. D Anderson cancer centers.
Two additional internationally recognized cancer centers located in Asia, and Europe, respectively have been added to our six five dash one to one with one already opened for enrollment.
Both sides were selected for their expertise with tumor types of interest to Farnborough.
With a total of four sites, we expect to rapidly determine our P. Two D and move into the cohort stage.
Although expectations of clinical efficacy a low in the dose escalation stage as specific histology of interests are not required in the protocol investigators are permitted to enroll patients with relevant and tumor types.
Okay.
In the O six five dash, one or two study of oral <unk> in leukemia is we have dosed the first patient in the dose escalation part and will update our progress as dose escalation continues.
Details of this study were described in our recent press release.
To summarize similar to the solid tumor O six five dash one O. One study the initial dose escalation stage of the leukemia trial will determine the recommended phase two dose followed by a proof of concept cohort stage.
Or if I draw will be evaluated in patients with various hematological malignancies and leukemia subtypes. These include a M. L. C. L. L. M. D. S and also specific leukemia subtypes dependent on their fifth three kits or Mark Kaye pathways.
In our six five dash one O two three cohorts will receive oral farnborough as a single agent and the rest in combination with the nine o'clock.
Or hyponex, letting agents or low dose Ara C.
The basket cohort enrolled patients with biomarkers relevant to Fad, razmak monism, but diagnosed with different hematological malignancies or benign hematological conditions characterized by uncontrolled proliferation.
The protocol allows for expansion of the cohort based on efficacy, which may allow for acceleration of the clinical development and registration plan for <unk>.
As a reminder, encouraging anti leukemic activity and good tolerability in AML and CLO patients who are observed with the IV formulation of Hydra dosed intermittently in combination with <unk>.
Let us now turn to 140, a novel orally available P. L. K one inhibitor.
Having filed the I N D with the F. D. A we expect to open a phase one slash two study for the treatment of solid tumors in early 2022.
Who will provide details of the cohorts to be included in the study at that time, along with our dosing strategy for 140 as a single agents.
This strategy is strongly supported by our preclinical data, which shows that 140 is biologically differentiated from the other P. O K one inhibitor in development.
Specifically preclinical studies by a secular cell and collaborating investigators have demonstrated sensitivity of certain tumor types in patient derived specimens to 140 monotherapy given as daily oral dosing.
If these findings are produced in the upcoming clinical studies 140 could emerge as a promising alternative in multiple solid and liquid cancers.
The expansion of clinical programs for our two lead candidates is building up to a very exciting period for cyclists out.
By the end of the first quarter of 2022 we expect to have three ongoing phase one two clinical trials, which taken together should result in one of the most data rich periods in our company's history.
As these datasets begin to mature the positioning of phaedra.
Relative to other development stage CDK inhibitors is worth considering.
The success of first generation CDK drugs, such as Pfizer's eyebrows have attracted the attention of both drug developers and investors.
Several new therapies are now in clinical development targeting a variety of CDK enzymes.
We thought it was important to discuss on today's call Hafod raise differentiate it.
Okay.
Effective anticancer drugs must be capable of durable target engagement.
While our previous intravenous formulation of Hydra clearly demonstrated strong single agent activity. We also recognized that intermittent or a weekly dosing of an IV administered drug would not be convenient for patients, especially in the midst of it I'm going to pandemic.
We therefore invested a considerable time and resource studying the pharmacokinetic relationship between oral and intravenous phaedra.
These data were presented in October 'twenty, 'twenty and shows that our oral formulation had similar bioavailability to the IV formulation, including half-life maximal concentration and area under the curve.
This led us to conclude that further could be optimally dosed as an oral daily schedule therapy.
With a four hour half life and the once or twice daily dosing, we believe world Farnborough is capable of durable target engagement, but with the added benefit of oral dosing convenience for patients.
As a highly selective inhibitor of both CDK to an city canine fodder can help restore apoptosis within a cancer cell in two important ways.
By targeting CDK nine fighter inhibits the transcriptional regulation of anti apoptotic proteins, such as Mcl, one and Mick.
By targeting CDK to further addresses an escape mechanism when city canine is inhibited and also directly inhibits self proliferation by preventing overexpression of cyclin E.
When it is abnormally elevated cyclin E contributes to resistance of several tumor types, mostly in the women's cancers to various anti cancer therapies.
We believe that fibers dual targeting both within the cell cycle pathway may confer a competitive advantage in the clinic.
In the months ahead, we hope to formally present many of these exciting findings featuring our two lead drug candidates.
Having reviewed the progress with our clinical programs and ongoing research activities I would like now to turn the call over to Paul Mcmoran for review or cycle ourselves third quarter financials Paul.
Thank you Spiro.
As of September 30 of 2021, cash and cash equivalents totaled $42 million compared to $43 6 million as of June 2021.
The decrease of $3 4 million was primarily due to $6 3 million net cash used in operating activities offset by $2 9 million cash provided by financing activities.
Research and development expenses were $4 2 million for the three months ended September 32021.
As compared to $1 1 million for the same period in 2020.
R&D expenses relating to Farnborough increased by approximately $2 5 million for the three months ended September 30 of 2021 due to the opening of the two phase one two clinical studies.
And clinical supply manufacturing.
Additionally, R&D expenses related to C Y C 140 increased <unk> 5 million for the quarter as the preclinical evaluation and clinical trial supply manufacturing C Y C 140 progressed.
Okay.
General and administrative expenses for the three months ended September 30th 'twenty, 'twenty, one or $1 8 million.
Compared to $1 5 million for the same period of the previous year.
Due to increased legal and professional expenses.
And recruitment costs relating to the expansion of the clinical team.
United Kingdom Research and development tax credits were $1 million for the three months ended September 32021.
As compared to $3 million for the same period in 2020.
Due to the increase in R&D expenditure elavil for the tax credit.
Net loss for the three months ended September 30th 'twenty, 'twenty, one was $5 million compared to $2 3 million for the same period in 2020.
The company estimates that the cash resources will fund currently planned programs through early 2023.
Operator, we are now ready to take questions.
Okay.
At this time, if you would like to ask a question.
Press Star one now on your telephone keypad again that is star one on your telephone keypad to remove yourself from the queue you May press the pound key.
One moment, while we queue.
We'll take a question from Jonathan Aschoff of Roth capital.
Oh, Hi, guys. Congrats on the clinical progress and then I had a couple of questions. What must you first learn and the factory sick with solid tumor and leukemia programs to know if the pivotal trials must be randomized or single arm.
Would that just be something tiley learn from your own trials or could there be something from competing drugs something they could deliver that would influence in FDA opinion on that.
Jonathan. Thank you for your question I think Mark you be the best person to answer that.
Single randomized studies please.
One question that I'm looking forward to having to deal with.
Okay.
We have enough activity in a given tumor type.
For a pivotal trial.
Which I believe is possible.
I think it really the answer to your question really depends on which tumor response. So it depends on the type we are kind of biasing the trial towards a relapsed refractory disease.
For most of these situations we believe.
The single arm trial will be adequate to go for great for rapid breakthrough designation.
If it is a space we're going earlier.
More upfront.
The lines of therapy, then we would probably be required to do a randomized trial, but right now our focus is on a number of them.
Potential areas, where it would be a single arm study.
Okay I'm guessing the answer is going to be the same if I were to ask the same question for 140.
I guess it makes sense guys any better sense other than the first half of 2022, which was as per your last slide deck for when we might see the first solid tumor data for Patrick.
Yes, I think we can speculate on that obviously would be keen to report responses with durability, which needs says Tampa follow up we are very optimistic about that N T.
Proof of concept study, but who may be surprised to the upside. If this were to occur in the dose escalation phase as I mentioned in my prepared remarks. It is not our expectation since 80% of the patients in dose escalation and get the drug below our pizza or do you typically do see response and it also hinges on the physician's enrolling patients.
With tumors of interest.
Should that happen I wouldn't see a response of course that could be very exciting for both the company and the drug and we would certainly wish to announce that at the appropriate time.
Okay. Thank you guys.
Thank you Jonathan.
And once again that is star one on your telephone keypad, well move next to Qunar, Russia of Brookline capital.
Hi, Thanks for taking my questions and also congratulations on all the progress.
With regard to the site looks like got you helpful sites onboard.
So will some of these are digital sites be participating in the dose escalation phase.
And also how quickly you think you can start enrolling patients in the proof of concept casino. Once you have a sense of are they.
The effective dose.
Thanks for your question Mark would you like to take that as well please.
Yes, sure. So at least four sites are actually a couple of things one.
A portion of the trial.
There will be additional sites.
Increase the numbers in speed for the for the phase two.
<unk>.
So we anticipate this move.
Very quickly.
Hi.
Forget enthusiasm as you can see from the timelines here.
All of our cohorts accrue pretty much the moment they open.
Things are looking very good.
And.
You know depending on how much.
How well the drug is tolerated.
That will determine the number of dose levels that we have but the way. The trial is designed is that immediately.
We reached our phase II dose, we will roll right into the into the various phase two trials. So.
As we said we have four trials, we have four sites now that are in the United States and global.
And we're adding will be adding a number more clear when we get to the phase II component was the study also high level sites like this.
Okay and also in the proof of concepts that triad.
Now one of the indications there are more patients showing up what are some of the indications you will continue to enroll them and follow their model is there a cutoff in terms of how many patients you're going to enroll in terms of each of these indications.
Hello.
This design.
You know, we'll also see that information as we accrue so.
And it says they will vote with their feet I think some arms will obviously accrue better than others, certainly areas, where our responses machine all of course.
You know probably wanted to this is that the investigators really know and the phase one what we're thinking about it in the phase two so we really will get some preliminary proof of concept in the phase one because some of those types of tumors will be accrued so I think that well.
The responses.
We will drive the accrual so we have that flexibility.
Yeah.
The arms, if we need to if things respond in the basket for example.
And we will go from there.
Okay.
I add some color if I may to Mark's reply, so that the audience are I know you're more familiar but the audience niche to understand some of the dynamics driving enrollment which is obviously a critical.
First of all it's not SaaS fore sight. After six groups are pursuing the few available slots in the dose escalation study for which we're about halfway through now there's the two phase one units at city of hope and MD Anderson.
As well as the two lymphoma departments, who are part of this study. These are all open we have just mentioned that we opened our fifth group and our third site phase one units as well as what is the final I'll cite a final. So there's one group who will join towards the end of the year. The last two non U S centers were picked because other expert.
Ts and specific cancer types that are part of the phase II design.
So in some ways the way I would like to answer your question or was that already jumping ahead to starting in a way and enrolling tumors of interest by definition of who these people typically get to see in their practice.
The reason, we took them into the phase one portion is because the strong desire to get into this study early which I think underlines marks remark about excitement from the investigators we typically assume half a patient per center per month of the industry as a typical a benchmark you enrolled six patients since July which suggests to US that this is gonna go quite faster than the typical benchmark.
So for all these reasons, we feel that once we know the recommended phase two dose. These are moves very fast into the middle stage, where proof of concept can be expected.
Very exciting times.
Yeah, that's great.
And in terms of C y C. One five P M.
You are just waiting for the 30 days to Paas, what else needs to be done to start the trials there.
That's essentially correct Kumar I think the F D. A to review the file if they have no questions. At 30 days. We will then open the study for enrollment we already have the sites lined up I believe theyre already patients being proposed for this study, which means that once we open or should be able to enroll and we have a lot to learn about 140, but it wasn't a similar.
With Sabra, both I and DS went through the FDA review with no question. So if you have a similar experience we should expect towards the turn of the year to start enrollment.
Yeah.
Okay, great. Thanks, so much.
Thank you Kumar.
And once again to ask a question that is star one on your telephone keypad, one moment, while we queue.
And we'll move next to Kevin the greater of Oppenheimer.
Hi, This is actually Susan calling in for Kevin, but I have just two questions.
The first question on <unk>.
So you mentioned that you want me to follow the patients for certain period of time.
<unk> showed durability of response.
As long as they tolerate the drug they can receive it.
So.
We don't have a theres no set time limit on the amount of drug that can get.
So if it takes them several months to have a full response.
But we are we are providing drug for that but the minimum time for treatment to be eligible in the studies 20 days.
Got it that makes sense.
Yeah. My second question is actually on track with our 140.
How really histology of interests selected for the collaborative preclinical studies.
Did you guys have other evidence.
Or to initiating these studies.
First of all we have not initiated the 140 or a program yet that will happen as I've said very shortly after the NDA review by Mark can certainly address the question of how the prospective histology so of which only two have been disclosed publicly.
This is a breast and colorectal have been or will be selected mark over to you.
Uh huh.
And in very brief answer we do extensively into the biology I mean, some background on me I was.
Actually it was an investigator in academia in this field.
Back in my days at city of Hope.
So I notice this area very very well.
On it.
So there are a number of tumors that are driven by U P. L. K, one it's either amplifies or it is believed to be part of the.
Activity pathways that drive the tumor so.
Looking at the known biology, there there is also preclinical data.
This group has has done and published in the past that suggest certain tumors are more sensitive.
We're very sensitive to this to this mode of action, So I think between that and getting them a very high level team of investigators working with us both pre clinically and clinically so between all of them. That's the trial design that we have that we've just submitted to the FDA.
Think that we have an optimal group of potential.
Potential tumor cells.
But most importantly.
As the Science Hill as it often does.
We have a basket of unbilled in the studies.
If new tumors are identified that may be sensitive because it's a mechanism that can be enrolled into the basket.
And if the responses seen in the basket than those tumors come out as an individual cohorts towards the registration pathway.
So we pretty much cover all bases.
In summary, we have many in mind that we think will respond.
Have preclinical data for <unk>.
And then we are open for other ones.
The data in the future come out to support that pathway.
Yeah.
Susan let me add a bit more color to Mark's.
Reply to your question, which May also be helpful for the audience as we mentioned earlier in our remarks, we believe there is a biologically different implication for a while how 140 works. It does hit okay. One that's as primary target as other drugs have or had in the past, but it does work very differently it appears and asthma.
Explained just now once this information is publicly disclosed we will be providing additional color on the selection of tumor types is that mechanism is well understood and biology as one of its clinical practice and therefore would guide us to select additional tumor types at the time that the studies open. So we're very much looking forward to that it's only a few.
Weeks away if things go according to plan, we should be able to have this discussion again.
If not sooner than certainly at our next quarterly call.
Uh huh.
Okay. That's very helpful. Thank you I'll jump back in the queue.
Thank you Susan.
And at this time I'd be happy to return the call to management for closing remarks.
Yeah.
Thank you Leo and thank you all for participating and cycle ourselves third quarter 2021 call.
I think it is evidenced that we are building significant momentum across our clinical programs with ongoing enrollment in our phase one two study of <unk> in solid tumors and the initiation of the phase one two trial for FA leukemia, we remain on track to achieve our milestones and deliver on the <unk>.
Shots on goal over the coming quarters.
In addition, we plan to initiate the phase one two study of 140 <unk> in solid tumors in early 2022, followed by 140 in leukemias.
I had all these events, we would like to thank our shareholders for their continued support and we look forward to updating you on our progress and meeting some of you at upcoming conferences, either virtually or in person.
Operator at this time you may end the call.
Yeah.
This does conclude today's conference call you may now disconnect your lines and everyone have a good day.
Yeah.
[music].
Yeah.