Bio Green Med Solution, Inc. (BGMS) Q1 2020 Earnings Report, Transcript and Summary

Good afternoon, and welcome to the Cyclacel Pharmaceuticals First Quarter 2020 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 Jan Medina, Investor Relations for Cyclacel Pharmaceuticals.

Good afternoon, everyone, and thank you for joining today’s conference call to discuss Cyclacel’s financial results and business highlights for the first quarter ending March 31, 2020.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 first quarter of 2020, 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 first quarter 2020 business update call. First and foremost, we hope that all of you listening to our webcast are safe and well.The global pandemic caused by COVID-19 disease continues to affect nearly all human activity and creates uncertainty in every business sector. The events of the last few months have made it clear that we need novel science-based solutions to emerge from the crisis.At Cyclacel we take our social responsibility very seriously in particular protecting the health and safety of our employees, the patients we served and the communities in which we live and work.As indicated in today's press release, we have taken relevant protective measures and our following government orders with our employees mostly working from home. We’re working closely with clinical trial sites to ensure adequacy of clinical supplies and that are trials are following specific FDA guidance during the pandemic.We have been advised by clinical investigators that they continue to screen and register patients in our studies and remain on track with enrollment. At the same time, we cannot assume that circumstances such as a second surge will make it more difficult for patients to remain on or join our studies.Cancer patients faced increased risks in this environment. As we design new dosing schedules and subsequent protocols we are therefore considering such matters as frequency of visit and translational research requirements.Despite these challenges we are committed to our mission of serving cancer patients and maintaining the integrity of our clinical research. Cyclacel's business strategy is to build an innovative pipeline addressing the rising problem of cancer resistance.We are studying the ability of our agents alone and in combination with other drugs to improve anticancer effectiveness and treatment outcomes. We are pleased to report continued progress and will briefly describe on today's call our plan for advancing a lead drug fadraciclib.Based on current spending plans we estimate that our pro forma cash and equivalents of $27.3 million including the spring equity raise, will provide a cash runway to the end of 2022. So we'll first review fadraciclib formerly known as CYC065.Fadraciclib is a novel CDK inhibitor targeting the CDK2 and 9 isoforms which act as key components of their p53 pathway. Activity against CDK2 results in reduction of cyclin E and again CDK9 in suppression of MCL1 levels.Cyclacel is evaluating Fadraciclib as a single agent in patients with solid tumors and in combination with other drugs in patients with hematological malignancies. Overexpression of cancer resistance proteins or amplification of oncoproteins such as MCL1 or Cyclin E respectively are associated with cancer cell evasion.MCL1 one is one of the 10 most frequently over expressed cancer genes and is a member of the BCL2 protein family including BCL2, BSL1, BCL-XL and others which act as pro-survival mechanisms for cancer.Cyclin E, a protein encoded by the CCNE gene is over expressed in several gynecological cancers including breast endometrial/uterine and ovarian. Addiction to cyclin E enables cancer cells to escape death by the cancer treatment.Suppressing this proteins forces aberrant cells into apoptosis or programmed cell death. Cyclacel therapeutic strategy is to suppress transcription of such proteins and reactivate the apoptotic machinery leading to cancer cell death.Recent discoveries of the importance of MCL1 have resulted in a race to bring to market MCL1 suppressing medicines. We believe that Fadraciclib is a leader in this race based on demonstration of durable suppression of the protein in peripheral blood mononuclear cells and anticancer activity as monotherapy in heavily pretreated patients with solid tumors.MCL1 suppression was observed in the majority of patients enrolled at the Recommended Phase 2 Dose or RP2D in part one of our 065-01 dose escalation study using a sparsely administered schedule. We enrolled 26 patients who received Fadraciclib as a single four-hour infusion every three weeks.Nearly all patients who achieved stable disease with tumor shrinkage had molecular markers relevant to the drugs mechanism including MCL1 cyclin E and/or MYC amplification. We have enrolled a further 22 patients in the ongoing part two of the study with a more frequent dosing schedule of one hour infusion on days one, two, eight and nine every three weeks.Escalation in part two has reached the fourth dose level and additional patients have been enrolled to establish RP2D. As previously reported a patient at the fourth dose level with heavily pretreated MCL1 amplified endometrial cancer achieved radiographically confirmed partial response or PR after a month and a half on Fadraciclib.This patient is continuing on study after approximately nine months on the same dose. After the last restaging shrinkage in her target human lesions has improved to 79%. Another patient was cyclin E amplified ovarian cancer achieved stable disease with tumor shrinkage of 29% after four months of Fadraciclib monotherapy.Based on Fadraciclib's clinical activity durable suppression of MCL1 and extensive preclinical and clinical data on overexpression of cyclin E in various cancers we plan to further explore Fadraciclib in a tissue agnostic, precision medicine driven study evaluating patients with gynecological cancers.The concept behind this study broadly follows the precedent-setting approval of pembrolizumab in microsatellite instability high or mismatch repair cancers. Briefly, we are planning a phase 1/2 open label parallel cohort study design.The initial sample size is 60 patients with each cohort enrolling 20 breast endometrial/uterine or ovarian cancer patient respectively. Patients will receive Fadraciclib monotherapy and subsequently combination therapy depending on available options.Details of the trial will be forthcoming after consultation with experts. Primary endpoint would be Objective Response Rates or ORR and duration of response would be an important secondary endpoint. Successful ORR performance will be measured against benchmark response rates.Once it has started in early 2021 we expect enrolment of this study to take approximately one year notwithstanding pandemic delays. In addition to intravenous administration of Fadraciclib we are evaluating an oral capsule formulation. We have dose three patients and reach the second dose level.Initial pharmacokinetic or PK data demonstrated a predictable PK profile closely overlapping that of the IV administration with encouraging exposure levels. In our hematological malignancies program we have opens two dose escalation studies to test the hypothesis that suppressing MCL1 and BCL2 can result in anticancer activity against relapsed or refractory leukemias.We are evaluating a Fadraciclib and venetoclax combination in patients with relapsed refractory AML or MDS in the 065-03 study and relapsed or refractory CLL in 065-02. Reflecting the unmet need for alternative AML treatments we have rapidly enrolled 11 patients in 065-03, the primary endpoint of which is determination of RP2D and safety.The rationale for AML study is that MCL1 plays a dominant role and is supported by the clinical evidence of synergy of Fadraciclib and venetoclax in inducing apoptosis. This suggests that double hit suppression may be more beneficial than suppressing either protein alone.Heavily pretreated patients received a combination of oral venetoclax and escalating doses of Fadraciclib on a four-hour infusion schedule once every two weeks. We have reached dose level five with two patients on 200 mg/m² where approximately 300 to 400 mg total dose of Fadraciclib and venetoclax in combination.Tumor license syndrome or TLS was reported in both patients consistent with anti-leukemia activity related to the drugs mechanism. This follows previously reported reductions of leukemic blast in the peripheral blood of patients treated on lower doses with a combination.Based on these findings we plan to evaluate additional more frequent dosing schedules. In the CLL, BCL2 overexpression is the main feature and MCL1 is an escape mechanism, leukemia cells especially in the lymph nodes may stop responding to venetoclax followed by relapse often associated with MCL1 overexpression.Eradicating CLL in lymph nodes and achieving minimal residual disease or MRD negativity is an important treatment objective. In the 065-02 enrollment thus far has been slow reflecting the long relapse free survival after frontline CLL therapy.Given that eventually a large number of patients will relapse, investigators have advised Cyclacel to persist as an unmet medical need is emerging. In order to increase enrollment we have implemented certain protocol amendments and open to new sites in addition to MD Anderson.Five patients have been treated so far after dose level four or 150 milligrams per meter squared. The first two patients failed ibrutinib therapy and one of the two also failed CAR-T. They were dosed once every two weeks at 64 milligrams per meter square or Fadraciclib and venetoclax as per label post ramp, for five and six cycle respectively which was well tolerated.Both patients had continuing shrinkage of their lymph nodes and one was MRD-negative after five cycles on the combination. Both of these studies are part of our risk sharing alliance with the University of Texas, MD Anderson Cancer Center whereby MD Anderson assumes patient costs for all studies and we provide investigational drugs and other limited support.The MD Anderson Alliance also includes clinical trials with our other programs sapacitabine and CYC140. In our DNA damage response program we are enrolling patients with relapsed or refractory AML or MDS in part two of our 682-11 study with sapacitabine, our nucleoside analog.This dose escalation study has enrolled 12 patients and is evaluating safety and effectiveness of an oral combination of sapacitabine with venetoclax. In addition an investigator sponsor trial or IST is enrolling at Dana Farber Cancer Institute evaluating a combination of sapacitabine with olaparib, AstraZeneca Lynparza in patience with BRCA-mutant breast cancer.In our anti-mitotic program we're evaluating CYC140, a polo-like kinase or PLK1 inhibitor which like Fadraciclib was discovered in-house. Five patients with advanced leukemias have been recruited to 140-01, our first in human single agent dose escalation study.No dose limiting 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. Like many peer biopharma companies we have responded to society's call by volunteering our medicines for testing and indications where they may be helpful to patients affected by the corona virus.To this end we have recently announced a collaboration with the university of Edinburgh to evaluate the potential of our CDK inhibitors, Fadraciclib and seliciclib for reducing runaway inflammation in acute lung injury in patients with COVID-19 disease.In addition two ISTs at Cedar Sinai Medical Center and the University of Newcastle are evaluating seliciclib our first generation CDK inhibitor in patients with Cushing's disease and rheumatoid arthritis respectively.During the quarter we laid the foundations from multiple data outcomes over the next two years. As we continue executing our strategy and advancing our clinical development programs, our upcoming key milestones include report updated Fadraciclib, Phase 1 safety and efficacy data with frequent IV dosing schedule in patients with advanced solid cancers.Report initial safety and PK data from Phase 1 study of Fadraciclib oral formulation. Treat first patient in Fadraciclib Phase 1/2 precision medicine driven studies. Report initial data from Fadraciclib, venetoclax Phase 1 study in relapsed refractory AML or MDS and CLL.Report initial status CYC140 Phase 1 first-in-human study in relapse/refractory leukemias. Report initial data from sapacitabine, venetoclax Phase 1 study in relapse/refractory AML or MDS. In report data from Phase 1b/2 sapacitabine olaparib IST in BRCA mutant metastatic breast cancer when reported by the investigators.With capital on-hand estimated through the end of 2022 we have the resources to deliver key milestones in our clinical studies.I would not like to turn the call over to Paul to review our first quarter 2020 financials. Paul.

Thank you, Spiro. As I find in today's press release for the quarter ended March 31, 2020 cash and cash equivalents totaled $8.9 million compared to $11.9 million as of December 31, 2019. The decrease of $3 million was primarily due to net cash used in operating activities of 2.8 million and point 1 million of net cash used in financing activities.The company raised net proceeds of approximately $18.4 million from an equity financing in April 2020. And we estimate that cash resources as of March 31, 2020 together with the 18.5 million net equity financing will fund currently planned programs to the end of 2022.Research and development expenses were $1.1 million for the three months ended March 31, 2020, as compared to $1 million for the same period in 2019. Expenses relating to our transcriptional regulation program increased by approximately $0.3 million for the three months ended March 31, 2020 as we continue to progress the clinical development of Fadraciclib.General and administrative expenses for the three months ended March 31, 2020 were $1.3 million compared to $1.2 million for the same period of the previous year. Total other income net for the three months ended March 31, 2020 was $0.9 million compared to $0.1 million for the same period of the previous year with the previous year.The increase of $0.8 million for the three months ended March 31, 2020 is primarily related to income received under an asset purchase agreement with Thermo Fisher Scientific. United Kingdom research and development tax credits were $0.3 for each of the three months ended March 31, 2020 and 2019.And our net loss for the three-month ended March 31, 2020 was $1.2 million compared to $1.8 million for the same period in 2019. Following the April equity financing, our common stock outstanding is 4.9 million shares.Operator, we are now ready to take questions.

[Operator Instructions] Our first question is from line of Jonathan Aschoff with Roth Capital Partners. Jonathan?

Thanks. And good afternoon guys. I was wondering given the increased effort for fadraciclib in solid tumors. Could you describe the solid tumor landscape potentially addressable by the drugs such as breast cancer, after let's say CDK4/6 inhibitor failure or something like ovarian cancer after platinum failure or Park inhibitor eligibility? And then after that what might you consider to combine fadraciclib with in with in cyclin E overexpressing solid tumors if monotherapy is not close enough?

Jonathan, thank you very much for your question. The landscape for gynecological cancers is evolving, but the important clinical data has been reported in recent months. For example, regard to the first part of your question in breast cancer, this is of course hormone receptor positive breast cancer which is nearly three quarters of the entire breast cancer population, the standard of care is CDK4/6 inhibitor together with hormone therapy. Drugs like palbociclib, ribociclib and abemaciclib.When CDK 4/6 inhibitors fail, the primary correlate for resistance to this activity of this type of class of drugs is over expression or amplification of cyclin E. This was shown in Pfizer's PALOMA-3 study with palbocilib two ASCOs ago. So we know that the vast majority of patients who receive standard of care, this is the combination of hormonal therapy and CDK4/6 will eventually fail this therapy combination and will overexpress cyclin E. So this is clearly a very important subset. We estimate from literature citations that approximately a third of this hormonal receptor positive population will present with cyclin E amplification.It may take a few years. I remember the fadraciclib was launched in the U.S. in 2015 before we see that, but we're now starting to see it. So resistance to CKD4/6 plus hormone therapy inhibition is a very important marketplace and literally more than 50,000 patients available based on our modeling to address with the cyclin E amplification reducing therapy like fadraciclib. Now in terms of combinations I will ask Judy to comment on this population before I go on to discuss ovarian cancer. Judy?

Okay. So I think our strategy is really try to combined it with one of the hemotherapy they commonly used in a population of patients who have failed the front line. As you know that we basically have three types of hormonal therapies. The oldest one is tamoxifen, then we have aromatase inhibitors and also the estrogen receptor degraders to surge. I think that our plan is to combine with one of those into patients who have failed the 4/6 inhibitor front line hormonal therapies.

Thank you, Judy. So the second part of your question was about ovarian cancer and what to combine with, that landscape is an even more flux. We just saw literally a couple of days ago a new approval for PARP inhibitors. This is addressing patient's not only who are potentially BRCA-mutant after testing, but possibly have HRD homologous recombination deficient disease and has now been proven, but in the subgroup of patients who are HRD positive and possibly also BRCA positive, that PARP inhibitors, either alone or in some suitable combination of high levels of activity. Yet they tends to not have extremely long durability. Most patients tend to progress after about a year.In the subgroup of patients who are HRD negative, a new standard of care appears to be emerging which is that of Avastin or bevacizumab based on recent data. And its not entirely clear whether frontline ovarian cancer maintenance with PARP inhibitors in HRD negative patients have the same benefit for patients as Avastin based therapy may.But of course one could combine PARP inhibitors and bevacizumab, Avastin to achieve some disease control. However ovarian experts are telling us that the vast majority of patients who are never offered PARP inhibitor therapy possible because they have insensitivity to platinum typically have cyclin E amplification. So with estimate of addressing population about 27,000 patients with the high-grade serous ovarian -- type of ovarian cancer which is the lion share of this disease who will present with not being suitable or not being candidates for either platinum and/or PARP inhibitor therapy. And a third of that as I mentioned approximately 27,000 patients in total, addressable market by a drug that can regulate cyclin E amplification. So Judy could you answer what might be possible continence in the ovarian cancer setting particularly for patients who are not suitable for PARP inhibitor therapy.

Well, I think this is a question that certainly we need to have further discussion with ovarian expert in the field. As you know that traditionally we consider, we treat patients with platinum if initially they were platinum sensitive. So I think that should we be combining and looking at the price sensitivity department and then retreat them and with a combination of 065 for planning, that was one example or some other agents that commonly used in very refractory settings.

Okay. Thank you. I have one more question. Just wondering what's has been going on with the COVID-19 program since its April 20 announcement?

Thank you, Jonathan. We can certainly give to you and to our audience an update on that collaboration. As you all know from the press release some days ago the University of Edinburgh published research starting in 2006 and with subsequent papers in 2012 and 2014 showing that in three different animal models of lung injury ranging from acute lung injury to fibrotic disease, to pleurisy there are appears to be anti-inflammatory activity of seliciclib first-generation CDK inhibitor. They further localized this inflammatory activity on effects on activity neutrophils. Neutrophils is this antenna family activity on effects on activated neutrophils neutrophils are of course an important part of the immune system but after inflammatory injury such as the one caused by this bleomycin induced models of lung damage can produce overactive neutrophils.The need to be directed to apoptosis or they're came across cause massive inflammatory cascade problems often times called cytokine storm. In addition a group from Dana Farber Cancer Institute in Boston published data at about the same time many years ago showing that seliciclib is also active in slowing down the rate of adhesion of myeloma cells when attaching to bone marrow stromal cell. Again another inflammatory cascade hallmark in the context of myeloma which is of course a cancer of the blood. They have also demonstrated in that set of experiments and xenograft models that seliciclib the transcription also regulates the transcription of interleukin 6. Interleukin 6 is found in post-mortem studies of COVID-19 patients to have been a major prognostic factor and the rapid decline.So for this reason the University of Edinburgh is keen to first of all demonstrate whether the same observations apply to fadraciclib our new CDK inhibitors that has not been tested so far in models of inflammation. If they see a systemic effect then perhaps this is a class property and I would certainly encourage them. Assuming that they are confident what we have is reproducible they would like to go on to a exploratory medicine study which could probably a big University of Edinburgh possibly other centres who collaborate with them under the auspices of a UK wide effort to stop COVID a program called stop target which is funded by both charitable and government sources. So although we're not an inflammation company and we'll say an oncology company this is our area of expertise who are very keen to help and to the extent we can also in addition to helping patients potentially learn more about our drug. This is for us a win-win effort

Thank you very much guys.

Thank you, Jonathan.

And next, we have a question from Wangzhi Li with Ladenburg. Your line is open.

Hi. Thanks for taking my question. Could you hear me?

We can hear Vangzhi, hello.

Okay, good. So, I follow update. The first question is regarding the fadraciclib single agent IV dose escalation. Maybe I miss it, but I wonder what dose level you are now? It's still the 213 or is higher now?

So you're talking about the fadraciclib Phase 1 study in solid tumors. Is that correct?

Correct.

Okay. So this is the 065-01 part to study. We're testing a frequent dosing schedule. And I will let Judy to maybe describe what we see at 213 and what happen next. Over to you Judy.

Yes. We're still at the 213 milligram level. We're not going above it.

Okay. So that will be the dose level for the precision tumor trial?

The precision tumor trials will be using the part two dosing schedule.

Is it will be the 213 milligram dose or is it different dose?

Well, I think that once we come about this, that it's going to be the recommended Phase 2 dose it will either 213 milligrams or when dose level lowered if we -- when we expand the 213, the trends is not tolerable. But so far that it is tolerable. We don't have excessive dose limiting toxicity. We have some patient required dose reductions, so we still in phase of sorting that out. So we don't have excessive dose limiting.

Okay. Got it. In terms of the data reporting timing of the data report, should we still needed 2020 or maybe a little bit late because of COVID-19?

Both the principal investigators in the Dana Farber Cancer Institute program with whom we been doing our Phase 1 studies both for the IV an the oral, I came to publish the results. We have had those discussions with them. There are two conferences to the end of this year. Major oncology meetings. We don't know if they will be held physically or virtually, but somehow they will be held as we have seen with the ACR and soon with ASCO. So we expect by end of 2020, Wangzhi, we'll have that data available in a peer review setting.

Got it. And then shifting gears to the oral formulation. You have three patients so far, looks pretty consistently the IV formulation. I'm just wondering how many dose levels. How patient you need to see to really say, think that the oral formulation can placed the IV combination?

Okay. So first of all, we have indeed, as you said, three patients; one at 75 milligrams flat dose and two at 150. So we are still a little bit below when we expect to be with the IV formulation given that we're using exactly the same schedule, but this time with an oral capsule Phase 1, 2, 8 and 9. Let me ask Judy about her expectations with a caveat that is still early in the oral development.

Well, it's always a bit challenging to predict between the two formulation. I think the good news is that the PK of the oral looks favored. And I think that we are close. We may be able to go up at windows level, but I don't think would be have to go up a lot, because the bioavailability is pretty good.

Okay. Got it. And my final question is on the CLL trial. You saw two MRD negative response now. I just wondering what do you thing at the bar of ORR or do you are for setting to give you a competence to avenge these further in the CLL setting?

This is great question. But I think we are still in a dose escalation study, which was the first we ever did with this combination. The primary endpoint for this study is recommended phase 2 dose and safety. So I don't think that this party was designed being that most patients will get the drug at lower doses to determine efficacy. We're still learning as to what the properties of the combination are. But I think we mentioned in the CLL setting in our press release and previous communications patients do very well on frontline regimens whether there are BTK inhibitor based, chemo immunotherapy based or even combinations of the venetoclax with anti-CD20, they tend to last for at least two or three years before relapse. More than 85% of patients would relapse because most of them will survive that initial period.o there is a large repository of relapse patients to treat once they fail frontline therapy. Once we wait for the patients to fail all available therapies then come to a phase one study things are sometimes very hard. So it's really hard to benchmark at this point Wangzhi what the right level of response as well as duration of response would be. We are encouraged by the MRD negativity observed certainly concomitantly with reduction in lymph node size which appears to be sustained on the combination even if the patients were sensitive to the venetoclax alone, they clearly did not achieve MRD negativity on the venetoclax alone with where the patient was persuaded to stay on treatment.But I would call those exploratory findings. I don't think we are yet at a level where we can give the drug consistently and start to make projections on what would be a suitable level of activity, let alone duration, and therefore design I suppose ultimately a randomized study in CLL. First thing is to define our RP2D and we think we are close. We're now at 150 milligrams per meter square which is of course much more than one giving in solid tumors, but consistent what we have in AML. So as an AML, we're topping around 200 milligram per meter square, we're not too far. So we should be able by the end of this year to get to the primary endpoint of his study and then start defining next steps.

Got it. Thanks a lot for answering by questions.

Thank you, Wangzhi.

Our next question in from line of Kumar Raja with Brooklyn Capital Markets. Kumar?

Thank you for taking my questions. So with regard to the tradition medicine approach, what would be the strategy in terms of company and diagnostic, development of company in diagnostic sphere. And in terms of what are the expectations in terms from ORR and DOR? And obviously based on the genetic background office population what are your expectation in terms of regulatory strategies there. We will see like based on the genetic background you can go ahead and get a approval based on that. How pickup trial do we expect going forward ?

Kumar, thank you for your multiple questions and of course and of course they're addressing a lot of important issues which we are not yet ready to address because we don't have enough data. But let me pick on the first few and then Judy will discuss regulatory strategy and other options. I think we very seriously and diligently thinking of the companion diagnostic strategy. There are however some important differences. In solid tumors at least in the large US tertiary referral centers most patients get screened via NGS next-generation sequencing. So it's possible to determine the status of cyclin E and/or MCL1 by doing NGS profiling in these patients. And therefore we don't need the classic prior for example BRCA assay to determine a patient suitable for PARP inhibition some three or four years ago.Certain important distinction is the state of technological evolution in determining genomic status in patients advanced by leaps and bounds in a short time. We know that there are some needs to have standardized centralized testing and would like to explore them further with potential investigators and that will determine how we'll move forward. But we feel comfortable that at least we can determine the status of amplification of a protein and baseline by using NGS data. Ultimately in solid tumors I want to have follow-on assessment of genomic status, but this would be quite challenging particularly in the area of COVID-19. He cannot easily ask a relatively young patient with gynecological cancer to come in and give more about specimens to determine that. That will have to be determined along the way, but certainly to determine patient's a baseline seems to be feasible if this is done routinely.In terms of overall response rate and duration of response benchmark, of courses this could be different by cohort. We have some pretty good ideas of what those are in breast cancer and ovarian cancer based on the subgroups we discussed before. But as you Judy mentioned this need to be validated by KOL dialogue, which is ongoing. And we have to learn a little bit more about the rapidly evolving landscape in endometrial / uterine cancer which has a lot of new options, but none that appears to be compelling as both its incidents and poor survival continue to be feature of these disease. It's probably the only women's cancers that has increasing mortality over the last half a decade or so. So it remains very big unmet medical need. So these are important questions will be better placed to answer them once with more precisely define eligibility criteria for our precision medicine driven study and that will happen in the second half of this year then we'll be able to give more color. Let me ask, Judy to comment on your other question about regulatory strategy.

Well, thank you. I think the regulatory strategy, I consider that pretty straightforward and by which I mean that if we have sufficient single agent activity that in a refractory population that could be identified by either MCL. When amplification or cyclin E then the response rate defined -- certain magnitude of response rates will suffice and I think you probably already see the precedent in other FDA approval we're talking about something probably around 15% that range and higher than that that would be certainly right good and we need your abilities. Well, that's just what the precedent is. I think for regular approval after study's approval is probably required randomized studies.And this is where the questions of combination chemotherapy comes in. And there are two ways to think about combination therapy. One is to have two drugs that actually both are active together but they don't have overlapping toxicities, completely one single agent alone. For example, if -- I'm just using example variant cancer if one would to choose to combine with platinum, whether it's cisplatin or carboplatin you know that predominant toxicity of platinum is neurotoxicity -- cisplatin and myelosuppression especially from a cytopenia with carbo, then for CYC0065 certainly, we have not yet seen any toxicity at all. Your hypothesis would be both for active and you benchmark that against departing along. In patient who has departing along in patient who has the chance to respond cisplatin because they previously have responded to cisplatin. And of course the second hypothesis is based on messiness of action where they're reducing MCL1 were actually chemo sensitized themselves to certain chemo therapies. Now that I think is something that we don't have any improve of in the clinic until we do the randomized studies. So I hope this answers your question.

Yes, it does. And maybe one more question with regards to the enrollment in the clinical trials. You guys mentioned early on you are still continue to screen and involve patients. So from what time line of this, like is it for recent? And what differences are you seeing in terms of various sites, because like some states are opening up and some states are still closed. So what kind of differences are you seeing in the site? And maybe you can talk a little bit with regard to the FDA guidance and what kind of changes are being made in some of monitoring the patients were already on the trial?

Thank you, Kumar. I'll take the first part of your question and Julie will handle the FDA guidance that recently came out due to COVID-19. So in terms of regional enrollment, our primary locus of enrollment is Boston, Dana Farber is of course and Houston where MD Anderson is. We have not seen dramatic decline. We know that Boston is an epicenter of the pandemic and yet there appears to be some downward slope in the curve based on reported new infections. It appears that Dana Farber as one of the many hospitals in the Harvard Medical Complex is somewhat less affected in that Mass General is the primary referral center for COVID-19 patients. There was recently an article in the press about reduction in chemotherapy of Dana Farber. It was in the LA Times and it pegged it at 15%. Obviously, our drug is not chemotherapy, so we're not at this point encountering issues, but it's hard to say how things will go if there was a second surge late in the year for example that is a risk factor.Houston has been relatively spared in relative terms compared to our New York New Jersey area Boston and Seattle, but it remains of course of concern. MD Anderson has imposed restrictions on access. They have control entry, few entrance system before and complete prohibition of unnecessary visits and no family and so on. But so far we have been able to continue to enroll, patients are being screened and enter into our studies because they're faced very poor prognosis. I don't think anybody on this call is unaware of the very short survival that AML patients can expect, so that becomes a very serious problem for these patients if they are not receiving treatment or being considered for potential investigational trials.In our CLL study, as we mentioned we have two new sites both of those on the mid-Atlantic region. They are not in a major metro area like Washington DC or Philly so they are so far not in input exposed to risks from the virus as of this moment we don't know how this will move forward, but so far they have been able to enroll their respective patients, so this study continues. So in relative terms we have been spared. There's hard to predict how the future will go, but for instance we have stopped pursuing a dialogue with European investigators. Europe is in the midst of the pandemic. They are going to have to first of all demonstrate that they can safely handle go back to work over the months to come before we can consider opening studies there. And we have also slowed down the possibility of adding new sites in the U.S. until we further understand the trajectory of the pandemic pretty much along the lines of what you described. So with that let me turn to Judy to address the regulatory question.

Well, I think the FDA guidance that is really trying to provide some framework how to do the clinical study in this very unusual and challenging pandemic. So, I think the first of all is that if somebody who doesn't need to be in the hospital then they don't need to be in the hospital. To me that criteria is not terribly relevant to the population patients that we try to target. You know that when you fail the multiple line therapies you have refractory disease and the tumors growing I mean that it's a life and death issue. So it's not something you can sit on it and wait the four months until the COVID-19 cases go down.What we have seen is that that the sites are getting better because we work with major sites and with major sites and to pre-screen the patients and really try to be more specific in and making sure if they do come in they're eligible. And instead of just taking a lot of patients, screen them and then three of them says what, I have something else, they don't call. They're doing it much careful job so I think that's good news. And the second is that in terms of how we monitor we work with the sites very closely and we have been anyway with phone calls and so that to us is remains the same. In terms of the tradition of monitoring, I'll be honest that we see a -- most of the sites we work with are allowing us to access their medical charts remotely due to the endemic. So that is helpful to us you directly get you the source to making sure that data captures are accurate.

And at this time I'm assuming we have no other questions on the phone lines. I'd like to turn it back over to Spiro Rombotis for any closing remarks.

Thank you, operator and thank all of you for participating in Cyclacel's first quarter 2020 earnings call. And your ongoing support of our efforts to deliver on our strategy to realize stockholder value by demonstrating safety, efficacy and cost effectiveness of our pipeline assets. We look forward to updating you on our progress and meeting although virtually some of you at upcoming conferences or the annual meeting. Please stay safe. Operator at this time you may end the call.

Ladies and gentlemen thank you for joining us for today's call. You may now disconnect.