Good afternoon, and welcome to the Cyclacel Pharmaceuticals Third Quarter 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’ll now 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 third quarter of 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 third quarter of 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 third quarter business update call. Our vision at Cyclacel is the translator understanding of cell cycle control biology into medicines that will improve the life of cancer patients.

We approached this by exploiting transcription or regulation and DNA damage response pathways to discover novel drugs that overcome cancer resistance to treatments. Our business strategy is to develop a pipeline of innovative medicines and realize stockholder value by demonstrating their safety, efficacy, and cost effectiveness.

Cyclacel’s work in cancer drug discovery started with our founding scientist, Professor Sir David Lane, a global authority in cell cycle biology, who discovered p53, a key tumor suppressor gene that malfunctions in about two-thirds of people with cancer.

Under his guidance, our drug discovery programs concentrated principally on cyclindependent kinase inhibitor and in particular CDK2/9 isoforms, which operate as key components of the p53 pathway. These efforts resulted in advancing our transcription or regulation program into the clinic with our lead drug CYC065 and novel CDK2/9 inhibitor.

CYC065 works by suppressing Mcl-1 a pro-survival protein member of the Bcl-2 family. Bcl-2 proteins help cancer cells survive onto cancer therapy, gain and advantage of a normal cells and ultimately confer resistance to cancer treatments.

The Mcl-1 suppression strategy has attracted a lot of attention in the scientific and from a surgical communities and a competitive race is ongoing to bring to market drugs that suppress Mcl-1. Several human cancers including certain gynecological and lung cancers and certain leukemias are characterized by Mcl-1 overexpression or amplification.

Designing protocols to exploit this findings in Mcl-1 high patients is a potentially important therapeutic strategy. We believe that Cyclacel is a leader in this race as CYC065 has demonstrated durable suppression of Mcl-1 as monotherapy at tolerable doses in patients with solid tumors.

These previously reported Mcl-1 results were observed in the majority of patients enrolled as the recommended Phase 2 dose of 192 milligrams per meter square in part one of our CYC065-01 Phase 1 study in which CYC065 was given as a single four-hour intravenous administration every three weeks.

We have since been enrolling patients in part two in which CYC065 is given as four one hour intravenous administrations for the first two days or the first two weeks out of a three week cycle. Dose escalation has reached the fourth level at 213 milligrams flat dose.

We are excited to report that a patient with previously treated endometrial cancer and Mcl-1 amplification has achieved a partial response or PR by investigator assessment based on tumor shrinkage of 48%. The PR was achieved after four cycles of CYC065 at 213 milligrams.

After the first two cycles, the patient achieved stable disease with tumor shrinkage of 16%. A second patient with ovarian cancer and Cyclin E amplification treated with two cycles of CYC065 at 213 milligrams also achieved stable disease with tumor shrinkage of 19% for investigator assessment.

Subject to confirmation by follow-up scams, this finding suggests that a frequent dosing schedule of CYC065 may be a preferred strategy to suppress shortly of transcripts such as Mcl-1.

In parallel, with intravenously administered parts one and two, we have began part three of the study with an oral formulation of CYC065 and treated the first patients at 75 milligrams flat dose. Based on preclinical data and pharmacokinetic data from this first patient, we expect good oral bioavailability.

We plan to report next year initial safety and PK data for the oral form and updated safety efficacy in mechanistic data for the IV dosage form. Let us now turn to CYC065 studies in patients with hematological malignancies. Preclinical data have demonstrated great potential for combination strategies suppressing both Mcl-1 and Bcl-2.

In particular, preclinical data by Cyclacel scientists and external scientists have demonstrated synergy of CYC065 in combination with venetoclax. Venetoclax, the first approved Bcl-2 inhibitor is an important therapeutic advanced approved for first or second line CLL, either alone or with an anti-CD20 antibody.

More recently, FDA granted accelerated approval for venetoclax in first line AML unfit for chemotherapy in combination with hypomethylating agent or an nucleoside analog. Venetoclax treated patients eventually stop responding and this is often correlated with Mcl-1 amplification.

We have therefore open to dose escalation clinical studies to test to help offices that’s suppressing both Mcl-1 and Bcl-2 can result in anti-tumor activity against relapsed or refractory leukemias, where specifically evaluating the combination of CYC065 and venetoclax in patients with relapsed or refractory CLL in the CYC065-02 study and in patients with relapsed or refractory AML or MDS in the CYC065-03 study.

In the CYC065-02 study enrollment has been slow with two patients with relapsed or refractory CLL treated so far. Both have failed ibrutinib therapy and received treatment for four and six cycles respectively with a combination of CYC065 and venetoclax, which was well tolerated.

In CLL leukemia cells in the lymph nodes stop responding to venetoclax and cause eventual relapse. Eradicating lymph node disease by a combination of CYC065 and venetoclax is therefore an attractive strategy toward achieving a cure for CLL. Lymph node assessment by radiographic imaging may provide important clues on the value of the combination.

Both CLL patients had shrinkage of the large lymph nodes by CT scan on the combination of venetoclax and CYC065 dosed once every two weeks at 64 milligrams per meter square. According to the investigators, the reason for slow enrollment CYC065-02 is at CLL patient are doing very well on frontline regimens without relapse.

They advised that Cyclacel is persist with the study is eventually patients with relapse and the large unmet medical need will arise. In view of these facts, our strategy has been to open additional CLL sites and implement certain protocol amendments to increase enrollment. Two new U.S. sites have been opened and others are in discussions.

Meanwhile, we are exploring the possibility to increase the magnitude of dose escalation based on safety information from our AML study, 065-03, which has been enrolling better. Despite recent developments in AML, including the venetoclax approval, an unmet medical need remains in both relapsed refractory AML and MDS.

We have now treated eight patients in 065-03 and have escalated to 150 milligrams per meter squared of CYC065 dosed once every two weeks in combination with venetoclax. Unlike CLL, where Bcl-2 over expression is the main feature in AML, Mcl-1 plays a dominant role.

The rationale for this study is supported by a preclinical evidence confirming synergy of CYC065 and venetoclax in inducing apoptosis suggesting that double hits suppression of both Mcl-1 and Bcl-2 respectively, maybe more beneficial than suppressing either protein alone.

We are encouraged by investigator reports of decreasing blast in the first peripheral blood of patients treated with CYC065 in combination with venetoclax. We anticipated reaching the MTD from this study in 2020.

In our second program, we are enrolling patients with relapsed or refractory AML or MDS in part two of a Phase 1/2 study 682-11 evaluating the safety and effectiveness of an oral combination of sapacitabine, our nucleoside analogue, with venetoclax.

The clinical data published at the 14th European Hematology Association Congress supports 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 that is relapsed or refractory to prior therapy, such as cytarabine or hypomethylating agents.

Venetoclax has accelerated approval as front-line therapy in AML, in combination with hypomethylating agents or cytarabine, both of which are intravenously administered.

Combining sapacitabine with venetoclax may, therefore, offer an effective oral treatment regimen for patients who have failed front-line therapy, where venetoclax is already approved. In our third clinical program, we’re evaluating CYC140, a polo-like kinase or PLK1 inhibitor, which like CYC065 or discovered in house.

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

All four studies, CYC065-02 or CYC065-03, 682-11 and 140-01, are part of our strategic alliance with MD Anderson Cancer Center with the objective of evaluating three Cyclacel candidates in patients with hematological malignancies.

Under the terms of the alliance, MD Anderson assumes patient costs for up to 170 patients over three years in exchange for milestone payments up on first commercial sale for indications started in the Alliance. Cyclacel remains a sponsor for all of these studies. Let us now turn to our DNA damage response strategy.

Our goal here is to enhance the efficacy of standard of care by targeting inherited mutations in DNA damage pathways, such as homologous recombination or HR-deficient cancers, which include those with BRCA mutations.

The modest duration of clinical benefit to PARP inhibitors, the standard of care approved for certain gynecological cancers, including those with BRCA mutations, suggests a need for novel drugs used in combination to improve disease control and extend survival.

Sapacitabine works by an HR-deficient relevant mechanism that is distinct from the mechanism of action of PARP inhibitors. Sapacitabine has demonstrated durable activity in BRCA-positive breast cancer, including a patient still in remission after more than six years.

Recent clinical data with sapacitabine reported at the 2019 AACR provides the rationale for an ongoing investigator-sponsored trial or IST of orally dosed sapacitabine and olaparib, the leading PARP inhibitor approved for breast and ovarian cancer.

This IST is sponsor by the Department of Breast Cancer at the Dana-Farber Cancer Institute and is enrolling PARP inhibitor naïve patients with BRCA-mutant breast cancer. Cyclacel and AstraZeneca are supplying sapacitabine and olaparib respectively.

According to the investigators, a total of five patients with BRCA-mutant breast cancer, have been treated and one patient has achieved the partial response or PR. Three patients are continuing on treatments. We are proud of the company’s achievements in 2019, especially as we have established and leadership position in Mcl-1 suppression with CYC065.

We will provide further highlights of our progress at the upcoming ASH Conference with two presentations for our lead program CYC065 in AML/MDS and CLL and one for our sapacitabine 682-11 study.

As we continue executing our strategy and advancing our clinical development programs, our key milestones for the next 12 months include reporting on updated safety PK and efficacy of CYC065 Phase 1 data with frequent dosing schedule in patients with advanced solid cancer.

Initial safety and PK data for the Phase 1 study of an oral formulation of CYC065. Initial safety and efficacy data from the CYC065 venetoclax Phase 1 study in relapsed or refractory AML and MDS.

And the CYC065 venetoclax Phase 1 study in relapsed or refractory CLL and the sapacitabine venetoclax Phase 1/2 in patients with relapsed refractory AML or MDS. And the CYC140 Phase 1 first in human study in relapsed or refractory leukemias.

Also updated data from the IST Phase 1b/2 trial of sapacitabine, olaparib combination in patients with BRCA-mutant metastatic breast cancer, when reported by the investigators and determining the regulatory pathway and submissibility of sapacitabine in elderly AML patients.

With capital on hand, estimated until the end of 2020, we have the resources to take us through key clinical milestones in our ongoing clinical studies. I would now like to turn the call over to Paul to review our third quarter 2019 financials.

Paul?.

Thank you, Spiro. As outlined in today’s press release, for the quarter ended September 30, 2019, our cash and cash equivalents totaled $13 million compared to $17.5 million as of December 31, 2018.

The decrease of $4.5 million was primarily due to net cash used in operating activities of $8.3 million, offset by net proceeds from our common stock sales agreement with H.C. Wainwright of $4.1 million.

Research and development expenses were $1.1 million for the three months ended September 30, 2019 compared to $1.2 million for the same period in 2018. General and administrative expenses were $1.3 million for each of the three months ended September 30, 2019 and 2018.

Other income net for the three months ended September 30, 2019, was $0.2 million compared to $0.1 million for the same period of the previous year. The United Kingdom R&D tax credit was $0.3 million for each of the three months ended September 30, 2019 and 2018.

Net loss for the three months ended September 30, 2019, was $1.9 million compared to $2.1 million for the same period in 2018.

With the projected cash sparing benefits accruing from the MD Anderson Alliance, the company believes that cash and marketable securities, which were approximately $13 million as of September 30, 2019, will be sufficient to finance operations through the end of 2020. Operator, we are now ready to take your questions..

[Operator Instructions] And your first question comes from Wangzhi Li with Ladenburg..

Hey, thanks for taking my question and congrats on the progress of the quarter.

Maybe I missed it, but for the ASH abstract presentations, the abstract is only the trial kind of design and – but you mentioned you are going to presented data, so maybe any further color on how many patients data you can represents and what are going to data that represents at ASH presentations..

This is a question for Judy.

Judy?.

Well, we are trying to get a preliminaries on the patients who had been treated as you know that the CLL try, we have two patients. And sort of AML both at CYC065-03 studies, we have [indiscernible] we have about eight patients. So it’s a little tight, because they all came to find the past couple of months.

So we try to do get together data and hopefully to here assembles the preliminary safety and efficacy. And the same comments apply to CYC682-11 and we have….

Okay. And so for the AML trial, how about the dose level, I mean you had a eight patients to dose level.

What – which dose level you expect to see efficacy or activity?.

Well, that’s a very good question. And I think that based on the solid tumor study in a four hours infusions. We know that we have be able to durably suppressed Mcl-1 entity recommended Phase 2 dose of 192 milligram per meter square. So in the AML studies, we have just open the 150 milligrams per meter square foot enrollment.

So we’re hoping to hit 192 as pretty soon..

Okay, got it. Thank you. Last question maybe for the PLK1 inhibitor, can you provide any additional color on the enrollments, I think that you mentioned like two patients enrolled, essentially below to me, but maybe I don’t know the full details..

It’s enrolling not as fast as the 065-03, I think is that we have a total of three patients at this point..

Three days, okay. Okay, got it. Thank you very much for taking my questions..

Thank you, Wangzhi..

And there are no further questions at this time. I’ll turn the call back over to Mr. Spiro..

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

Operator, at this time, please, end the call..

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