Q4 2020 Forma Therapeutics Holdings Inc Earnings Call
Welcome to the former therapeutics fourth quarter and year end 2020 financial results and business update conference call. All participants are currently in a listen only mode of.
All of the managements prepared remarks, we will hold the Q&A session asked the question at that time. Please press the star key followed by the one on you touched on the telephone.
If anyone has difficulty hearing the conference. Please press star zero for operator assistance.
As a reminder of this call is being recorded today March 32021, I would now like to turn the conference over to Mario Corso. Please go ahead.
Okay.
Thank you Josh.
This is Mario Corso senior director of Investor Relations at forma.
Good morning to our listeners and welcome to today's call to review of fourth quarter and year end 2020 financial results and business update.
On this call I'm joined by frankly, our President and Chief Executive Officer.
Patrick Kelly, our Chief Medical Officer.
Dave Cooke, our Chief Scientific officer.
And Todd Shegog, Chief Financial Officer.
Before we begin I'd like to caution listeners that comments made on financial information provided during this conference call includes certain statements that are estimates beliefs forward looking and are subject to various risks and uncertainties any statements made during this call but are not statements of historical or current facts are intended to be forward looking.
Statements pursuant to the Safe Harbor provisions of the private Securities Litigation Reform Act of 1995.
We want to emphasize that such forward looking statements reflect our current expectations assumptions and currently available data regarding among other things our business operation development efforts regulatory strategy and relationships with third parties and are neither predictions nor guarantees of future events or performance.
Actual results could differ materially from those stated or implied by these forward looking statements due to the risks and uncertainties associated with our business, including those under the heading entitled risk factors in our annual report on form 10-K for the year ending December 31, 2020 being filed today and the.
Subsequent reports, including our quarterly reports on form 10-Q, and our current reports on form 8-K.
In addition, today, we will make a number of comments about our expectations for the COVID-19 pandemic on our business. We provide these comments to give investors insights into what we're observing however, given the dynamic nature of the pandemic there was a high degree of uncertainty.
Any forward looking statements made the company disclaims any obligation to update or revise any forward looking statements, except as required by applicable law.
I will now turn the call the all the call over to Frank our President and Chief Executive Officer.
Thank you Mario.
Good morning, everyone and thank you for joining us.
I am excited the house form as first quarter of the call and to provide an update on the strong progress. We've made over the course of 2020 as well as our plans for 2021.
Before I get started I'd like to express my deep gratitude.
So on patients investigators health care workers and employees.
Throughout the pandemic. So many have make tremendous sacrifices and demonstrated remarkable resilience.
The advance of science and to advance our mission to transform the lives of patients living with rare hematologic disorders cancers.
Today, we will provide updates on three development stage programs.
Following my opening remarks, our Chief Medical Officer, Pat Kelly will provide an update on F. T 42 to the PK or agonist being studied in sickle cell disease and.
The Luna side and on H, one inhibitor being studied in acute myeloid leukemia.
Liana.
Afterwards, our Chief Scientific Officer, Dave Cook, who will provide an update on FTE 71 of.
CVP P 300 inhibitor being studied in metastatic castration resistant prostate cancer.
Following a brief financial review from our Chief Financial Officer touch of God.
We'll be happy to answer any of your questions.
In 2020, we made strong progress in three important areas number one advancing our pipeline number two building our organizational capabilities.
And number three funding our future activities.
With regard to advancing our pipeline we reported at Ash in December the initial phase one results for our lead compound the ft 42, two and people living with sickle cell disease.
These data exceeded our hopes for the emerging profile of this potential foundational therapy in on.
Tober, we reported positive results of our pivotal trial for Luna side in the oven.
<unk> with relapsed refractory AML with the 98 one mutation.
Notably these results included compelling survival benefit in such a heavily pretreated patient population.
Lastly, we progressed ft seven years of do you want into the clinic.
With the phase one trial in late line patients with metastatic castration resistant prostate cancer.
This trial of broadly enroll late line patients, including those with ARV seven splice variant identified by genetic mutation analysis.
In January of this year, we reported first patient dosed in this trial.
With regard to building, our organizational capabilities, which strengthened our board of directors with three new appointments and also attracted top quality talent into the organization.
And collectively establish the culture centered on three guiding principles.
So on purpose people are why we succeed in.
Science drives this.
I'm proud of our culture and believe it will differentiate forma over the long term.
With regard to our funding of featuring the activities. We completed our successful initial public offering in June and the subsequent follow on equity offering in December.
This extends our current cash runway through the third quarter of 2024.
When I joined form of two years ago, we sharply focus our vision on being a leader in rare hematologic disorders cancers.
And it's been very gratifying to see the vision taking shape.
We now stand with three potentially transform the molecules in development.
With the towns the organization.
As well as a well capitalized company.
I'd like to now turn to 2021.
I am pleased to say 2021 is off to a strong start pro forma we reported today.
Press released the latest clinical data from our randomized multicenter placebo controlled trial phase one trial of Ft 42, two in people living with sickle cell disease.
These initial top line blinded results from the 600 milligram multiple ascending dose cohort are being reported as planned in the first quarter of this year. Despite the challenges associated with.
With the Covid pandemic.
We're pleased with the initial 600 milligram results and plan to report the full unblinded analysis in the upcoming scientific meeting this summer.
I'd like to touch on some key points number one while treatment assignment remains blinded. The initial results of the 600 milligram, Matt two cohorts support the 200 milligram of 400 milligram doses being evaluated in our ongoing phase III trial the hybrid.
The study.
Number two.
Doubling the dose of 600 milligram once a day for 14 days was well tolerated in patients with sickle cell disease with no dose limiting toxicity or treatment related adverse events identify.
Number three.
Hematology and chemistry parameters in the 600 milligram dose cohort were comparable to that observed with the 300 milligram dose previously.
Of note hematologic and hemolytic responses were typically burst at the end of the 14 day treatment.
Adjusting patients may benefit from longer duration of treatment beyond 14 days.
Shortly these data with the 600 milligram dose cohort of allowed us to continue moving forward with the next phase of this phase one trial.
The ongoing 400 milligram 12 week open label extension.
I'll now turn over the call of the path to discuss our ft 42 of two results in more detail as well as review of the loop side of it.
For relapsed refractory AML frankly on them.
Thank you Frank and good morning, everyone.
I'm and I'm delighted to provide updates on two of our programs F. T 42 O two for treating patients with sickle cell disease allele decided them for treating patients with relapsed or refractory AML with an idea of <unk> mutation.
F. T 40, <unk> is our oral once daily pyruvate kinase or PK R activator for which a pivotal phase III trial in more than 300 patients living with sickle cell disease is presently at world.
As Frank mentioned today, we are providing an update on the initial results from the patients who have completed the second two week daily dose cohort in our randomized placebo controlled phase one trial at $2 42 of them too.
As a reminder, on the trial design.
Each two week dosing cohort kind of roll up to 12 patients with sickle cell disease. However, based on our blocked randomization strategy a blinded blinded analysis can be performed after nine patients have completed the three week study participation.
A safety analysis that enables dose escalation decisions or to allow patients to enroll directly into our 12 week open label dose cohort.
Blinded data for the first nine patients enrolled in the 600 milligram cohort is the basis for our update today.
We are very pleased that this higher dose cohort supports a favorable tolerability profile similar to what we reported in the first 300 milligram multiple dose cohort as disclosed at the Ash meeting in December.
No treatment related adverse events or does limiting toxicities were observed based on these results. The 12 week open label cohort is now enrolling patients directly as the dose escalation portion of our phase. One study has closed the further patient enrollment.
It should be noted the based on the safety profile observed we could have continued to dose escalate if the protocol allowed us to do so.
However, our previous studies in healthy volunteers and in patients with sickle cell disease had led us to predict that the doses of ft 42 O to greater than 400 milligrams daily would not provide any additional PK on activation, which is the target of that of $2 42 hotels.
Indeed, the PK PD results from the 600 milligram cohort of confirm these observations, while we double the dose of Ft 42 of two to 600 milligrams daily over the previous 300 milligram daily dose.
Salt of near dose proportional pharmacokinetics response, we did not see a meaningful increase in the Pharmacodynamic response.
Specifically the increase in ATP levels in the sickle cell red cells was equivalent to what we saw in the 300 milligram dose cohort and there was only a modest decrease in the tier three dept levels compared to the prior experience.
These results further support the 400 milligram daily dose of Ft, 42 O two as the top the dose we are evaluating in the dose range of portion of our ongoing phase three registration trial.
While the more in depth per patient analysis can be anticipated once the 600 milligram cohort is formally unblinded.
We are able to look at the treatment effect of Ft 42 O. Two based on an analysis of those patients with detectable ft 42 of two PK, while continuing to maintain the study blind.
In the patients who were randomized to ft 42 O. Two we saw a similar level of clinical activity based on improved hematologic and hemolytic parameters as compared to the 300 milligram dose cohort.
This finding reflects the clear overlap of Pharmacodynamic responses between the two treatment groups.
Specifically all seven patients showed an increase in hemoglobin of of baseline with four patients achieving a one gram of greater increase.
Equally important all seven patients showing a reduction in the ridiculous sites compared to baseline with a median of 45% decrease.
Similar to the prior 300 milligram results all seven FTE 42 of <unk> treated patients had a reduction in bilirubin levels in LDH levels.
Overall, we continue to be pleased by the observes the by the observed safety and Tolerability profile at a dose level well above our intended phase two dose range.
The hematologic and hemolytic improvements observed with just two weeks of Ft 42 of two dosing is supportive of the concept that this mechanism of action can increase red blood cell health.
Supporting the potential for clinical for clinical benefit beyond hemoglobin improvement.
The hemoglobin response, coupled with the decline in your particular sites is early evidence supporting improved oxygen delivery to the tissues.
The reduction in markers of Intravascular Hemolysis is also encouraging we believe that these are leading indicators supporting the potential for a reduction in vascular damage and immune activation since it is well known that the interest cellular products released by Homolysis stimulus.
Endothelial cell immune cell activation.
Altogether the effects that we have observed on multiple service surrogate markers lead us to believe that.
At $2 42 of two administration may lead to the reduction of basal occlusive crises or voc's.
Pain events that require medical attention or hospitalization, which is one of the two primary endpoints in our ongoing phase III <unk> III trial.
Our phase III trial design reflects regulatory feedback and includes two separate primary endpoints, including hemoglobin change. Following 24 weeks of treatment, which is expected to support an accelerated regulatory filing and a 52 week rate of the ocs.
Which is intended to support full regulatory approval is positive.
This phase III trial is current as presently enrolling and we believe utilizes the optimal dose of ft 42, two as well as the appropriate trial design.
In summary, Ft, 42, O two was well tolerated and no safety concerns identified out of an exposure of approximately 50% over the anticipated exposure as planned in the ongoing phase II portion of our pivotal trial.
There was simple similar levels of biologic activity in the 600 milligram daily dosing cohort compared to the previous 300 milligram dose cohort once again supporting the selection of 400 milligrams daily as our top dose in our phase two dose ranging study as.
As well as the dose we are studying in the <unk>.
Ongoing open label 12 week dosing cohort.
As a reminder of this cohort will enroll up to 20 patients with sickle cell disease and it has allowed patients participating in the 600 milligram two week dosing cohort to rollover for which six of the initial nine patients in the 600 milligram cohort have done so.
A more detailed summary of all patients enrolled in the two week dose escalation cohorts as well as the initial observations from the 12 week 400 milligram open label extension.
Two of <unk> are expected to be disclosed in June likely out of scientific conference.
Now turning to allude deciding on mute.
<unk> inhibitor being evaluated in patients with relapsed or refractory acute myelogenous leukemia or AML.
In October of last year, we announced the interim analysis was successfully met in this registrational phase two trial in <unk> and an efficacy evaluable population of 123 patients.
We believe that the rates of complete remission or complete remission with hematologic recovery up 33% compares favorably to the current standard of care.
And while the median duration of the CR or CRH population has not been reached based on the sensitivity analysis. We know the median duration of the CR CRH response group to be at least $13 eight months, which we believe is of very differentiating factor of feature of elite of side of it.
In addition, among the CR or CRH responders the.
The 87% survival rate at 18 months in this heavily pretreated patient population is gratifying.
I will believe and we believe more closely resembles the results reported for earlier lines of the AML treatment.
The most commonly reported adverse events for primary primarily gastrointestinal nausea, and constipation with lab values, indicating increases in anemia neutropenia thrombocytopenia.
As well as transient liver enzyme elevations.
Differentiation syndrome, and adverse drug reaction in the class of target in this class of targeted therapies was also observed at a similar rate and with the outcomes as observed with other therapies.
Based on these data we are preparing a new drug application for an NDA to the U S. FDA.
Pharma has previously announced our intention to partner this program, where the company, having an established commercial capability and the sales force in place.
In the interest of time, I will not spend a great deal of time on nearly all of the them all but for all of the side of it.
But suffice it to say that we are as excited about this potential indication as we are for AML. The.
The phase <unk> data <unk> data presented at Astro last year demonstrated a preliminary disease control rate of approximately 50% and of heavily pretreated patient population with debt with predominantly enhancing recurrent <unk> mutant glioma.
Importantly, PK PD results have indicated that <unk> successfully penetrates the brain crossing the blood brain barrier, which is the necessary element for impacting tumor burden. In response, we believe that enhancing glioma represents a large potential commercial upside for the afore elite decided nib.
Due to the high penetration of the <unk> mutation in this patient population and the high unmet medical need.
With that I'm going to now turn the call over to Dave who will provide an update on ft, seven zero of five one or prostate cancer.
Thanks Pat.
Going to spend the next few minutes discussing our all CVP P 300 inhibitor ft, 751, which earlier this year began enrolling a phase one trial in metastatic castrate resistant prostate cancer or <unk>.
See RPC.
The CVT 300 is.
The required coactivator of androgen receptor driven gene expression.
751 has been shown to decrease expression of a R and it also inhibits dependent gene expression.
Additionally, CBP inhibition has been observed to inhibit prostate cancer cell proliferation in vitro and in vivo of patient derived xenograft model.
There is significant unmet need in MCR P. C. As the majority of patients eventually progress while on androgen deprivation therapy in combination with the adrenal androgen synthesis inhibitor aberrant around acetate or the androgen receptor agonist antagonist, such as the <unk> and Apple to the.
Mike.
Upon the failure of one of more of these regimens the therapeutic regimen leads to targeted chemotherapy and the five year survival rate for <unk> patients progressing on or after first line chemotherapy is estimated at only one 6%.
The mechanism of action of Ft, 751 is applicable to a broad range of resistance mechanisms, including the ARV seven splice variant, which lacks the hormone binding domain and for which there are no approved drugs.
The median survival for men with AB seven bearing on expression has been reported to the 10 eight months as compared to 27 two months for a wild type tumors. We believe that AB seven may be prevalent and approximately 20% to 40% of men after a second or third line treatment.
And this indication could represent an accelerated path to market.
In addition, we intend to explore ft $7 51.
The MCR PC with other mutation profiles.
And earlier lines of therapy.
As well as other air dependent tumors, such as triple negative breast cancer.
Following preclinical studies, showing the ft, $7 51 reduced histone acetylation and ER positive prostate cancers inhibiting the growth in prostate cancer cell line and show the antitumor activity in both <unk> sensitive and resistant prostate cancer Pdx mouse models, we began our first in human.
On trial earlier this year.
This trial will enroll up to 46 men with MTR PUC, who have progressed following one or more regimens with the adrenal androgen synthesis inhibitor antagonist or chemotherapy the <unk>.
While the utilizes an adaptive design starting with the dose of 25 milligram.
With titration to as many of five higher dose levels on a free week on one week off cycle.
Based upon pre defined safety and tolerability of measures.
Mutational status of circulating tumor cells on the profile, including <unk> splice variant expression and genotypic markers with the clinical assessment.
Including Psa levels and radiographic progression.
Depending upon enrollment rates, we intend to have initial clinical results from this trial in the second half of this year and a subset of patients.
The narrowly focused on safety Tolerability, PK, PD and preliminary biomarker data <unk>.
Results from the trial are anticipated in the first half of 2022.
Given the high unmet need in this population of men and a small number of innovative compounds with novel mechanisms in development. We are on a very intrigued by the promise of the ft $7 51, and we look forward to sharing initial data later this year.
I'll now turn the call over to our Chief Financial Officer Todd.
Thank you, Dave and thank you to everyone for joining us on today's call I wish to spend the first few minutes discussing our financial results for the fourth quarter and full year 2020, and then discuss our cash position and outlook on.
Our net loss for the fourth quarter of 2020 was $28 6 million and $74 million for the year ended December 31 2020.
This compares to a net loss of $24 7 million and $34 8 million for the quarter and year ending December 31, 2019, the increase in net loss during the year of 2020 was largely attributable to the absence of collaboration revenue, reflecting the complete.
<unk> of <unk>.
In 2019 of the performance obligations under our license agreements with Celgene now BMS.
Research and development expenses were $24 9 million and $93 4 million for the quarter and year ending December 31, 2020 versus 27.0 million and $111 3 million for the quarter and year ending December 31 2019.
This spending supports progress with all three of our compounds in development Ft, 42 O to allude aside of nib and ft, $7 51, including the start of our phase one and phase two three trials for Ft, 42 O two in sickle cell disease the.
The alluded side in the pivotal phase III trial in AML in phase one two trial in glioma and the progression of ft $7 51 into the first human trial in metastatic prostate cancer. These items were offset by a decrease in spending on internal research and.
<unk> expenses, primarily due to restructuring in January of 2019.
G&A expense in the quarter and year ending December 31, 2020 was $7 9 million and $30 8 million as compared to $6 8 million and $24 4 million in the quarter and year ending December 31 2019.
This increase reflects the costs related to being a public company, including stock compensation expense professional fees and insurance and aforementioned staff and additions to manage the expansion and clinical activities.
Our cash cash equivalents and marketable securities balance as of December 31, 2020 was $645 6 million compared to $173 2 million at year end 2019.
This includes net proceeds of $293 3 million received from our initial public offering in June of 2020.
And $258 6 million net proceeds from our follow on offering completed in December 2020.
Our current cash runway extends through the third quarter of 2024, which includes ongoing clinical trials as well as planned commencement of ft of 42 of two of development and thalassemia in the pediatric population.
Overall, we ended 2020 on a strong financial position and are well financed through important upcoming clinical milestones.
Josh we can now take questions.
Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw your question press the pound key please stand by we compile the Q&A roster.
Yes.
Our first question comes from Thiago <unk> with Credit Suisse. You May proceed with your question.
Great. Thanks for taking my question so.
Are there any noticeable of relevant differences to baseline characteristics of genotype became the subjects enrolled in the 300 milligram cohort versus the 600 milligram cohort I remember at least one patient and 300 milligram cohort.
How does slightly different presence.
Presentation of sickle cell and the follow up to debt, perhaps related to the open label study.
I understand it's a small sample size in a shorter period of time, but.
Should there be an expectation of seeing the signals related to potential benefits in the Vince or youll see I understand that's not really what the trial is designed to show.
But but wondering if we could see any signals that early.
Yes.
Thanks for the question Thiago was frankly here.
First of all these data are still blinded. So we can comment as best we can on the baseline characteristics.
And other questions. There so let me turn it over to Pat.
And respond to that.
Yes, I think in general the baseline characteristics of the patients is very similar to.
The 300 milligram cohort predominantly hemoglobin SaaS of genotype.
Patients being on Hydroxyurea.
Beyond so really I would say once we on buying more understand.
The treatment effect more specifically.
But at this time really nothing in the.
The stands out for your question related to the.
Patient populations.
And then in terms of the long term.
Aspects for the OC I think as we've always expressed that the 12 week will give us a lot more detail there with our additional exploratory studies that have been built into this protocol and as we mentioned some of the efforts to look at adhesion markers or inflammatory markers.
Overtime, we would expect that that's going to be.
Helping form.
More about the impact of <unk>.
What happens with such a profound reduction in the hemolytic markers in particular because of this translate in the.
On the background of.
In a relatively short treatment period of 12 weeks.
Does this continue to support our hypothesis that.
A less inflamed state has to contribute to an improved pace of inclusive outcome.
Got it understood. Thank you so much.
Thank you Thiago.
Yes.
Thank you. Our next question comes from Byron Amin with Jefferies. You May proceed with your question.
Yeah, Hey, good morning, guys. This is jeet Mukherjee on for Barry and thanks for taking the questions and congrats on the progress to date.
Was just hoping you could talk us through some of the heme parameters of you presented on the 600 Meg cohort today.
I think we noticed there was slightly fewer patients that were hemoglobin responders at 600, Meg versus 300, and it seemed as though LDH reduction was slightly lower as well. So I was just hoping you could maybe share a little perspective on that and also just on randomization I believe from your previous design you said it was either seven of two.
<unk> or 9% to three so just wanted to check if it.
It was consistent between the 300 and the 600 and of course thanks.
Yes, thanks for the question and before I turn it over to Pat.
The step back and say, it's really important to look at the totality of the data that we've been able to generate on 42 to the 700 milligram single dose the 300 milligram multiple ascending dose and the 600 milligram now multiple ascending dose in all of in a very rigorous and controlled way with placebo.
Controls multi centered so I'm going to give that as context and.
Overall, we're very pleased as we noted earlier about the totality of the data as well as the improvement in response and we're seeing over the 14 days of treatment. So let me with that turn it over to Pat.
Yes, so yeah, just the quickly to the randomization scheme of its the same so with the minimum of nine the randomization of 72, and where the maximum of 12 and all of the randomization would be 93.
It's the equivalent of analysis to the the.
300 milligram personal line patients dose there.
Just touching on what price that it's hard we don't.
Yeah, it's a difficult too with the small numbers to take.
Two the fact on the individual patient level, we of course will when we on line, we'll do that the jet and the general trends of everything everything is pointing on the right direction.
Again this of the two weeks study to just the intended to look at safety and understand some biology signals.
And what we're continuing to see is that evenly.
Even with just two weeks, we're seeing significant improvements in these parameters.
And many of them on at the end of treatment, which again our conclusion with the 300 is that it's quite likely we haven't actually reach the steady state in terms of buyout biologic response in this population in net.
The 400 milligrams for 12 weeks, just kind of give us much more insight in terms of.
Where are the where are the individual patient ultimately lap.
<unk> from a chronic treatment perspective, which of course is the goal here. This is a this is intended to be.
Foundational therapy, the patients will take.
For extended periods of time.
Got it. Thank you for the perspective, and maybe just turning to the OLED <unk> net program could you just maybe talk about your partnership efforts for that and in your view of what an ideal partnership looks like thanks.
Sure. Thanks, Thanks for that question.
The first as we mentioned earlier, we're very pleased with the the Luna side net of data that we reported in October many ways because of ash and everything else I.
We didn't get as much visibility out there with two of those data, but as you as you heard recently now from Pat.
It's really impressive to see the survival data at 18 months and so we're I think agents some good discussions can't comment.
On any of those at this point in time because of the nature of those kind of conversations, but I come back to the strength of the data.
And certainly a partner that has an existing infrastructure.
<unk> already with the portfolio of products. This one would be a nice wanted to put in there.
Thank you very much.
Thank you. Our next question comes from M&A on with Cantor Fitzgerald You May proceed with your question.
Hi, Thank you could.
Could you just walk us through your confidence here in the accelerated approval pathway based on hemoglobin response of 24 weeks based on your FDA interactions and then a follow up on the debt.
Of that 12 week, although the update what will be included in that initial update in the second quarter versus later in 2021 and am should we then expect to continue to get updates at the longer term follow up maybe later this year on into next year as well.
Yes. Thanks for the question on that so let me turn it to Pat there had been some questions about the accelerated approval process of Pep meeting coming on line.
Sure Yes.
We highlighted the study design for the Hibiscus study was put together last year with FCA input certainly as well as the European inputs the the <unk>.
Nope of the trial design is ultimately intended to generate a full approvals for the phase of occlusive.
Event rate of over a year for both the U S and the EU.
We continue to have conversations with the FDA around this program and they've been very supportive even from the get kind of that they wanted to.
Work with us on the studies, particularly as we've discussed with them our salad Simi of trial as well as our pediatric plans and.
We've had very direct conversations with them around the scope of the study and there is no indication from.
Our conversations on this that on accelerated approval pathway is closed in this indication certainly ox Friday of global blood.
Of cheese on accelerated approval path based on the hemoglobin response at 24 weeks.
And that path is still open.
Because there is no full approval in that space.
And so we are continuing to proceed with that and nothing has changed that.
On direction, particularly with discussions with the FDA.
In terms of the 12 week open label data side, it's we're rolling up the 20 patients directly enrolling as we.
Vacated.
We will provide an update at <unk> in June on the current.
The patients who are enrolling up to that point since its open label, it's less difficult in terms of data cuts and looking at the data.
But you could expect debt by the end of this year that with Pat that trial will be complete with full follow up on them.
So I would expect that at the end of this year, where you would also provide that.
The complete update on the on the totality of that data.
Thanks very much.
Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. You May proceed with your question.
Hey, good morning, and thanks for taking our questions.
Touching on one of the previous questions on on both slightly decreased and the hemolytic parameters of the 600 milligram versus third 300 milligram cohorts.
I'm wondering if this could potentially be indicative of Sip of auto induction as we've seen with.
One of the other PK all the activities out there any any thoughts on on potential mechanistic basis for the decrease or or is it really just.
In your mind day.
Small numbers of effect at this point.
Okay.
Yeah no. Thanks for the question.
It's definitely not the not related to any auto induction of pharmacology of the PK profile clearly showed the.
Expected C Max and AUC those proportional.
So no clearance issues with the drug.
I think it's it's literally just the.
Small numbers and are in the.
Potential variability that you might see amongst patients within with the just the two week of dosing.
The 12 week, but of the larger sample size is more likely to give us insights into where each of these patients and ultimately from a biologic response.
Okay.
Totally fair.
Also could you maybe give us an update on progress with the opening clinical sites in the <unk> trial.
And are there plans to provide any patient enrollment updates throughout the year.
Mark Thanks for the question so.
<unk> actively opening sites as we speak we haven't provided all of the site numbers.
Or enrolment numbers as of yet, but we are actively opening sites and enrolling patients.
Okay fair enough.
Under.
Just as a quick reminder, on that.
So as we talked about earlier.
We are.
The proceeding with the 200 on the 400 milligram doses.
Toward that Registrational phase two three so the 600 that we reported out today.
Certainly gives us.
Good I would say look at the characterizing the safety margin, which is what 50% over the top dose that we will be studying in the phase II III.
Understood. Thank you so much for taking the questions and congrats on the progress.
Thanks Mark.
Thank you and I'm not showing any further questions. At this time I would now like to turn the call back over to Frank Lee for any further remarks.
Well. Thank you everyone for taking some time to participate in today's call two.
2020 was a year of remarkable accomplishments performer and.
As evidenced by our news today on the second dose cohort in our multiple ascending dose trial of the 242 of two in sickle cell disease 20.
21, 2021 holds a lot of promise for continued strong momentum.
The R&D pipeline.
Just on rare hematologic diseases and cancers. So we look forward to sharing our progress on these quarterly calls over the course of this year.
Have a good day. Thank you all.
Thank you ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect.
Yeah.
Okay.
Sure.
Okay.
[music].
Yes.
Yes.
Yes.
Yes.
Okay.
Moving forward.
[music].
Okay.
Sure.
[music].
No.