Good afternoon, and welcome to the Cyclacel Pharmaceuticals Fourth Quarter and Full Year 2019 Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. After today’s call, members of the financial community will have an opportunity to ask questions.

[Operator Instructions] The company will also be accepting a limited number of questions submitted via e-mail to the address, ir@cyclacel.com. [Operator Instructions] 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 Cyclacel’s financial results and business highlights for the fourth quarter and full year ending December 31, 2019.

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 21E 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 Cyclacel does not take any responsibility to update such information.With us today are Spiro Rombotis, President and Chief Executive Officer; Paul McBarron, Executive Vice President, Finance and Chief Operating Officer; and Dr.

Judy Chiao, Vice President of Clinical Development and Regulatory Affairs.

Spiro will begin with an overview of our business strategy and accomplishments on Cyclacel’s multiple clinical programs, and Paul will provide financial highlights for the fourth quarter and full year 2019, which will be followed by a Q&A session.At this time, I would like to turn the call over to Spiro..

Thank you, Jan, and thank you, everyone, for joining us today for our fourth quarter and full year 2019 business update call.

We made excellent progress in the quarter and full year 2019 as total enrollment to-date in our company sponsored studies has exceeded 75 patients of which over 60 were treated with fadraciclib the new international non-proprietary name from the World Health Organization for CYC0065.Our vision at Cyclacel is the translate understanding of cycle control biology into medicines that can improve the life of cancer patients.

Our science strategy is to use insights into transcriptional regulation and DNA damage response pathways in order to discover and develop novel drugs that can suppress the ability of cancer cells to become resistant to treatments.

Our business strategy is to realize stockholder value by demonstrating safety, efficacy and cost effectiveness of our pipeline assets.Over expression of cancer resistant proteins or amplification of oncoproteins to which cancer cells become addicted, such as MCL1 or Cyclin E respectively increases the survival and or growth rate of cancer cells.

Cyclacel therapeutic strategy is to inhibit transcription of such label proteins, meaning that they are susceptible to pharmaceutical intervention.We believe that our pipeline of innovative medicines led by fadraciclib is well positioned to address the problem of cancer resistance through a precision medicine strategy.

Fadraciclib is a novel CDK inhibitor targeting the CDK2 and CDK9 isoforms which act as key components of the p53 pathway.Activity against CDK9 results in suppression of Mcl-1 and again CDK2 in reducing Cyclin E amplification.

Cyclacel is evaluating fadraciclib as a single agent in patients with solid tumors and in combination in Phase 2 hematological malignancies. Mcl-1 is a cancer survival protein and a member of the BCL2 family.

BCL2 proteins help cancer cells survive anti-cancer therapy gain an advantage over normal cells and alternately confer resistance to cancer treatments.The strategy of suppressing Mcl-1 has attracted a lot of attention in the scientific and pharmaceutical communities.

And intensely competitive race is in progress to bring to market drugs that suppress Mcl-1.

We believe that Cyclacel is a leader in this race, because fadraciclib has demonstrated durable suppression of Mcl-1 and anti cancer activity as monotherapy at tolerable doses in patient with solid tumors.These previously recorded Mcl-1 results were observed in the majority of patients enrolled at the recommended phase 2 does of 192 milligrams meter squared in part one of our 065-01 dose escalation study using a sparsely administered schedule.

In this part of the study which enrolled 26 patients, fadraciclib was given as a single four hour intravenous administration every three weeks.We have enrolled a further 20 patients in the ongoing part two of the study with a more frequent dosing schedule.

In this part, fadraciclib is given by one hour infusion on days one, two, eight and nine, every three weeks.

Dose escalation in part two has reached the fourth level at 213 milligrams flat dose.On our third quarter call, we were excited to report that a patient with heavily pretreated Mcl-1 amplified endometrial cancer had achieved a partial response or PR.

After two cycles of fadraciclib monotherapy 213 milligrams this patient achieved stable disease with tumor shrinkage of 16%.In the confirmatory scan, after four cycles on the same dose shrinkage of her target tumor lesions had reached 48%.

We are pleased to report that the patient is continuing on study after 10 cycles on the same dose and the investigators have recently assessed the tumor shrinkage at 73%.We also reported that a second patient with ovarian cancer and secondly amplification treated was two cycles of fadraciclib monotherapy 213 milligrams, had also achieved stable disease and tumor shrinkage of 19% per investigator assessments, and after four cycles a tumor shrinkage was assessed at 29%.These findings suggest that a frequent fast dosing schedule for fadraciclib may be a preferred strategy to suppress short lived transcripts such as Mcl-1 and or Cyclin E.

This is in contrast with the experience of historical CDK inhibitors previously reported to transiently suppress Mcl-1.For example, Flavopiridol, also known as Alvocidib was administered as continuous infusion, lasting either 72 hours, or 5 hours using a loading strategy.

In parallel, we have begun part three of our formulations given by mouth as fadraciclib capsules.

And reached dose level two after treating the first two patients at 75 and 150 milligrams flat dose.Pharmacokinetic or PK data achieved by oral fadraciclib capsules in the two patients demonstrated a predictable PK profile closely overlapping the early administration with encouraging exposure levels.We plan to report later this year initial safety NPK data for the oral form along with updated safety, efficacy and mechanistic data for the ID form.Let us now turn to fadraciclib studies in patient with hematological malignancies.

Preclinical data are demonstrated synergistic potential for combinations, suppressing both MCL1 and BCL2. In particular, preclinical data by Cyclacel scientists and external authors have demonstrated synergy of fadraciclib in combination with venetoclax.

Venetoclax a BCL2 inhibitor is an important therapeutic advance, it is approved for first or second line CLL either alone or with an anti-CD20 antibody.More recently, FDA granted accelerated approval for Venetoclax first line AML, and unfit for chemotherapy, in combination with a hypo methylating agents or nucleoside analogue.

Venetoclax treated patients eventually stop responding and this is often correlated with MCL1 amplification.We have opened two dose escalation studies to test the hypothesis that’s suppressing both MCL1 and BCL2 can result in anti-cancer activity against relapsed or refractory leukemias.

We are specifically evaluating the fadraciclib and venetoclax combination in patients with relapsed or refractory AML or MDS, in the 065-03 study and relapsed or refractory CLL in 065-02.

Despite recent developments in AML, including the venetoclax accelerated approval an unmet medical need remains in relapsed or refractory AML.A large number of investigational agents are currently in Phase 1 evaluation at tertiary care centers.

Unlike our historical experience with sapacitabine when AML patients would present with none or one line of previous therapy.

Today's relapsed or refractory AML patients present with 3 to 6 previous lines, including investigational immuno-oncology or IO combinations, which are associated with multiple facilities.Consequently, our expectations of strong anti leukemia activity are modest in this heavily preceded populations with poor prognosis, low performance scores and comorbidity.

Of note flavopiridol treatment of Leukemia is associated with tumor license syndrome or TLS in about 20% of patients.

TLS risk with venetoclax in leukemia is lower at about 2%.TLS results from rapid license and death of a large number of cancer cells which gum up circulation, increasing potassium and uric acid levels before the kidneys can remove them. For active management of TLS ranges from hydration to hemodialysis.

TLS is evidence that the drug works too well against the leukemia and that a shorter treatment effects may be preferable.Reflecting the unmet need for alternative AML treatments, we have rapidly enrolled 12 patients in 065-03 the primary endpoints of which is determination of recommended phase 2 dose and safety.

Heavily pretreated patients receive a combination of oral venetoclax and escalating doses of fadraciclib on a four hour fusion schedule, once every two weeks.We have now escalated to dose level five with two patients on 200 milligrams per meter square, where approximately 300 to 400 milligrams flat dose equivalent of fadraciclib.

TLS was reported in both patients consistent with anti-leukemia activity related to the drugs mechanisms.

This follows previously reported reductions of leukemic blasts in the peripheral blood of patients treated for lower doses with a combination.Based on these findings, we plan to also evaluate the one hour schedule associated with PR and stable disease in solid tumor patients, that 213 milligrams flat dose also in leukemia patients.

The rationale for the AML study is supported by the clinical evidence confirming synergy of fadraciclib and venetoclax in inducing apoptosis, suggesting that double hits suppression of both Mcl-1 and Bcl-2 may be more beneficial than suppressing either protein alone.In AML, Mcl-1 plays a dominant role.

By contrast in CLL Bcl-2 over expression is the main feature.

In CLL leukemia cells, especially in the lymph nodes, stop responding to the venetoclax, causing eventual relapse, which is often associated with Mcl-1 over expression.Eradicating disease in the lymph nodes and achieving minimal residual disease or MRD negativity by a combination of fadraciclib and venetoclax is therefore an attractive treatment strategy for CLL.In the 065-02 study a relapsed or refractory CLL, enrollment has been slow, reflecting the long periods of relapse free survival after first line therapies.

Given that eventually a large number of patient will relapse, investigators have advised Cyclacel to persist as a unmet medical need is emerging after relapse.To help increase the enrollment rates. We have implemented certain protocol amendments, open two new sites in addition to MD Anderson, and are in discussions with additional sites.

Three patients have been treated so far up to dose level 2 or 85 milligrams per meter squares.The first two patients are failed ibrutinib therapy and received the combination of venetoclax and fadraciclib dosed once every two weeks at 64 milligrams per meter squared for four and six cycles respectively, which was well tolerated.Both patients experienced reduction in lymph node size with one of them achieving MRD negative status.

In our DNA damage response clinical program with sapacitabine we're enrolling patients with relapsed or refractory AML or MDS in part two of a Phase 1/2 study. This 682-11 study is evaluating the safety and effectiveness of an oral combination of sapacitabine, our nucleoside analog with venetoclax.

The study design mirrors the accelerated approval of venetoclax with intravenous hyperventilating agents or a nucleoside analog as frontline therapy.However, in our protocol we evaluating patients with relapsed refractory disease, and both combination drugs are dosed orally.

Preclinical data published at the 14th, European Hematology Association Congress support the combination of sapacitabine and Bcl-2 inhibitors in AML. Based on prior clinical investigations sapacitabine is active and induces complete remissions in AML and MDS but as relapsed or refactory to prior therapy such as cytarabine or hypomethylating agents.

Combining sapacitabine with venetoclax may therefore offer an effective oral treatment regimen for patients who have failed frontline therapy where venetoclax is already approved.In our third antimycotic clinical program we're evaluating CYC140, the polo-like-kinase or PLK1 inhibitor, which like fadraciclib was discovered in house.

Four patients with advanced leukemias have been recruited to 140-01, our first in human, single agent dose esclation study. No dose limiting toxicities have been observed thus far.CYC140 is a small molecule selective PLK1 inhibitor that demonstrated potent and selective target inhibition in high activity in xenograft models of human cancers.

We are proud of the company's achievements in 2019 and in particular, establishing a leadership position in MCL1 suppressions.

We believe that the totality of clinical data collected to-date support pursuing a precision medicine approach to overcome cancer resistance with fadraciclib as monotherapy and in combinations.As we continue executing our strategy in advancing our clinical development programs.

Our upcoming key milestones include report updated Phase 1 safety, decay and efficacy data for fadraciclib. Utilizing a frequent IV dosing schedule in patients with advance solid cancers.

Report initial safety and proof-of-concept data from the fadraciclib venetoclax Phase 1 studies in relapsed refractory AML or MDS and CLL, report initial data from sapacitabine-venetoclax Phase 1b/2 study in patients with relapsed refectory AML MDS.Report initial data from the CYC140 Phase 1 first in human study in relapse refectory leukemia and report data from the Phase 1b/2 IST of sapacitabine olaparib combination in patients with BRCA mutant metastatic breast cancer when reported by the investigators.

With capital on hand estimated for the first quarter of 2021. We have the resources to take us to key clinical milestones in our ongoing clinical studies.I would now like to turn the call over to Paul to review our fourth quarter and full year 2019 financials.

Paul?.

Thank you, Spiro. As outlined in today's press release for the quarter and year ended December 31, 2019 our cash and cash equivalents totaled $11.9 million compared to $17.5 million as of December 31, 2018.

The decrease of $5.6 million was primarily due to net cash use and operating activities of $9.4 million offset by $3.8 million of net cash provided by financing activities.Revenues for the three months and year ended December 31 2019, were zero compared to $0.2 million for the same period in 2018.

The revenue is related to a collaboration, licensing and supply agreement with ManRos Therapeutics entered into in June 2015.Research and development or R&D expenses were $1.4 million and $4.7 million respectively, for the three months and year-ended December 31, 2019 as compared to $1.1 million and $4.3 million for the same period in 2018.R&D expenses relating to our transcriptional regulation programs, primarily our CDK inhibitor with fadraciclib increased $5.5 million from $2.5 million for the year-end December 31, 2018 to $3 million for the year ended December 31, 2019 as the clinical evaluation of fadraciclib progressed.R&D expenses relating to sapacitabine decreased $5.4 million from 0.9 for the year ended December 31, 2018, to $0.5 million for the current year, primarily as a result of expenditure related to drug supply manufacturers, not required in 2019.General and administrative expenses for the three months and year ended December 31, 2019 were $1.4 million and $5 million respectively compared to $1.5 million and $5.4 million for the same periods of the previous year.The company raised net proceeds of approximately $4.1 million during the year from its common stock sales agreement with H.C.

Wainwright. The company estimates its cash resources of $11.9 million as of December 31, 2019 will fund currently planned programs through the first quarter of 2021.Operator, we are now ready to take questions..

[Operator Instructions] Your first question comes from the line of Wangzhi Li..

Thanks for taking my question. Just one question about the Phase 1 trial in the solid tumor. In the previous part one you have a few patients with tumor reduction. Now you issue patient with the TR, and another patient with tumor shrinkage.

So maybe can you fully elaborate the difference between current dosing and the prior dosing and what you think indicating as dose response or is just because you're selecting patients based on the biomark?.

Yes. Hi, this is Judy. So I think it's a good question. And it's a little difficult to score it out definitively at this point. As you know that first of all, that's the part one patients who had tumor shrinkage was treated with a variety of dose, so that's a variable.

And the schedule is a little bit different than the 1-hour infusions that we have always increases more frequent. So I think we certainly very encouraged by the 1-hour infusions on days 1, day 2, day 8, day 9, because that it's a very clear it's a real partial response.

And second of all, it appears to be durable and the target lesions continue to shrink. So I think this, it's very encouraging..

Let me add more color on Judy's question we're not selecting for patients. These are all commerce studies for the investigators happen to be looking at next generation sequencing to look for molecular correlates, but this is not enrich study, not at this point..

Okay, got it.

So far, the 2 PR and reduction on the high dose, right cohort?.

That is correct. Both of these patients were treated with 213 milligrams. Judy over to you..

I think this is the dose levels, the highest dose level we have treated quite a few patients so far. So I think that certainly it's a bit more uniform with this group of patients, and both of them appear to in this group. So I think to that extent, I think it's very interesting.

But as Spiro said, we have not made a protocol requirement to preselect certain type of patients, because it's really a Phase 1 trial. So when they had responses, I think it's interesting to look at what kind of molecular marker signature in the tumor..

Got it. Okay. Thanks a lot..

Yes, Wangzhi, And thank you for your questions, so this is exactly where we are discussing in our comments. The potential for precision medicine strategy.

This would involve selecting for patients, as your question anticipated, which have the molecular markers MCL1 or Cyclin E amplification and enriching from different baskets perhaps in a tumor-agnostic context, much as we saw earlier in 2019, the FDA approval for pembrolizumab in different types of molecular selected patients is now a strong regulatory precedent for such a strategy.

More on that in the upcoming quarterly conference calls. But we appreciate your questions..

[Operator Instructions]. Judy, you have a question from the line of Jonathan [indiscernible]..

Thank you, I was wondering, what's clinical data support targeting Cyclin E amplified cancers, especially after the failure of our palbociclib CDK4, 6?.

Perhaps most relevant recent data reported ASCO is the PALOMA-3 study conducted by Pfizer, a sponsor of palbociclib. Whereas the PALOMA-1 established the PFS benefits and PALOMA-2 established an overall survival benefits for palbocilib in your positive to negative breast cancer patients.

PALOMA-3 asked the question or what is the molecular core profile of patient resistant to palbociclib. And they found that it was Cyclin E, not Cyclin D, which is a target of CDK4/6. But Cyclin E, the target of CDK 2. So for this reason, we feel there is a very large body of data, supporting Cyclin E amplification as a strategy.

And we expect to address that in our precision medicine plan that will come in the next few months..

And there are no further questions at this time. I would now like to turn the conference calls back over to the company for closing remarks..

Thank you, operator. And thank you all for participating in Cyclacel fourth quarter and full year 2019 earnings call and your ongoing support of our efforts to develop medicines to address cancer resistance and improving existing treatment options. We look forward to updating you on our progress and meeting some of you at upcoming conferences.

Operator at this time, you may end the call..

Ladies and gentlemen this concludes today's conference call. Thank you for participating. You may now disconnect..