Q4 2020 Metacrine, Inc. Earnings Call
Ladies and gentlemen, todays conference is scheduled to begin shortly please continue to standby. Thank you for your patience.
[music].
Ladies and gentlemen, thank you for standing by and welcome to the medical first quarter 'twenty 'twenty earnings Conference call. At this time, all participants lines are in a listen only mode. After the speaker's presentation, there will be a question and answer session.
And I ask a question day in this session you will need to press star one on your telephone.
Thank you and good morning, everyone earlier today, we issued a press release outlining our fourth quarter and full year 2020 financial results as well as our key clinical development milestones and the press release can be found on the new SEC.
And of our website at <unk> Dot com.
On the call with me today is our CEO, Dr. Preston Klassen, our Chief Medical Officer, Dr. Hubert Chen and our Chief Financial Officer, Tricia Milliken and will also join us for the Q&A session.
Today's discussion will include forward looking statements related to medical and its current plans and expectations, which are subject to certain risks and uncertainties actual results may differ materially due to various factors, including those described and the risk factors section of our most recent SEC filings.
These forward looking statements represent our views as of this call and should not be relied upon as representing our views as of any subsequent date, we undertake no obligation to publicly update these statements with that let me turn the call over to price them.
Thank you Pete and thank you all for joining us today I'm thrilled to be speaking with you on medicines first ever public call about the progress we've made throughout 2020 across both our business and pipeline and about the important milestones slated for the months ahead. We are fast approaching my one year anniversary as CEO and I'm as encouraged as ever at a significant opportunity with our ethics are.
Graham and Nash and by the potential of our scientific platform.
And medical we are driven by a vision of transforming human health by building, a sustainable vibrant biopharmaceutical innovator for patients with liver and Gi diseases and our.
Our focus is on the development of best in class programs that will help define standard of care for patients and their treating physicians and.
Our product candidates are targeted at the underlying pathophysiology of disease designed to be orally administered tolerable and easy for patients to take and are based on a deep and integrated understanding of disease biology, and small molecule chemistry.
Over the last year, we've achieved a number of milestones led by the advancement of our two novel FX or agonists met for a night and met 642.
Both of these agents have broad potential across liver and Gi disorders, and our initial focus is on advancing these candidates to address the critical unmet needs of patients with Nash.
On a highly prevalent liver disease today and is expected to affect up to 27 million people by 2030, and the U S alone and if left untreated Nash is a life threatening disease with a significant impact on patient outcomes.
Despite years of and researched by our industry. There are still no approved treatments for Nash today, we believe that and ethics or agonists therapy with the right benefit risk profile can play a foundational role in treating this disease, both as monotherapy and combination with other agents specifically because the ethics are mechanism addresses all of the key aspects of Nash pathology.
And it's well established that affects our activation can positively impact steatosis inflammation and fibrosis, the last of which best correlates with disease progression and liberated morbidity and mortality.
We believe that it is important to activate ethics are in both the liver and intestine to maximize therapeutic potential and that Pixar is highly expressed in both Oregon and writes multiple liver and intestine specific mechanisms that ultimately impacts the spectrum of liver pathology that is present in Nash.
Now further to the success of it and it's a program for Nash, it's essential that treatment and be able to drive strong pharmacology and clinical activity, while maintaining a favorable safety and tolerability profile, particularly in terms of limiting both LDL change and pruritus and lastly, given that Nash is a chronic disease. We believe that oral once daily treatment is important to enabling treatment.
Adoption and long term use.
Our ethics, our program achieves all of these attributes and our in house expertise and ethics of our biology and nuclear hormone receptor small molecule chemistry has enabled the creation of and FX a platform from which we were able to generate multiple ethics, our assets and drive a differentiated profile of potent pharmacological activity, while minimizing the liabilities that had been.
And seen in essentially all other FX our programs tested in Nash patients.
Foundation of the differentiation behind out and ethics are candidates.
On a proprietary chemical scaffold originating from the lab of one of our co founder Dr. Ron Evans at the Salk Institute.
This fact, Jeremy and scaffold and the non bile acid structure, and a neutral chemical entity that lack the carboxyl acid moiety that it's present on other ethics are agonist structures. This unique structure drives differentiated target gene regulation and through our in house expertise and structure activity relationship. We've tweaked the scaffold further to dry potency and continuous.
Target engagement.
Hosting and sustained exposure, while minimizing peak to trough drug concentration, which may help mitigate side effects.
We believe that the combination of a unique gene regulation profile and sustained PK PD activity is what enabled our differentiation.
Both met four nine and met exports you are derived from this and chemical family and both agents have demonstrated sustained PK PD profile that we look for and a successful episodic treatment.
Net fortnight has shown strong evidence of pharmacological activity expressed at Liberty fat reduction with a reassuring safety and Tolerability profile in Nash patients.
We believe this profile is class, leading among FX, our programs and our second FX our asset metrics for two continues to look very promising as we drive towards characterizing its clinical profile in Nash and our second half of this year.
So I'll briefly walk through the progress that we've made with both of these programs and highlight how we intend to move into late stage development and Nash as well as plans to initiate work and additional indications next year.
Starting first with net fortnight.
Early in 2020, we reported 12 week data in Nash patients were met for nine demonstrated a mean relative decrease of up to 55% and liver fat from baseline with up to 93% of patients responding with a greater than 30% relative reduction in liver fat at the highest dose tested.
The level of liver fat reduction that's reported with met for Nike and this trial is as good as or better than that reported for all other oral mechanisms of action over a similar treatment duration.
Equally important is the favorable safety and Tolerability profile observed with met four nine, particularly at the 50 milligram dose with a low 16% incidence of mild to moderate Friday with no drug discontinuation and single digit increases and LDL cholesterol with no proactive management.
No other FX or agonists and development has generated this kind of profile and Nash patients to date over 12 weeks of treatment with <unk>.
Strength of debt profile supports met four nights potential to serve as both monotherapy and as a backbone of combination therapy, which we believe will play an important role and Nash treatment over time.
And to demonstrate the opportunity of our ethics, our assets and combination therapy at the end of last year, we expanded met four and nine development into a phase two a combination study with the <unk> inhibitor and packed with flows and in patients with type two diabetes and Nash.
These two indications coexist and many patients with abnormal liver fat content scene and up to approximately 70% of patients with type two diabetes and biopsy proven Nash and up to approximately 25% of patients.
Given this we believe that combining our investigational <unk> agonists with approved diabetes therapies that on their own have demonstrated some liver fat reduction is a strong mechanistic combination approach and it could over time become standard of care for these patients.
These combination studies, a 12 week randomized placebo controlled phase Iia clinical trial designed to evaluate the safety Tolerability and pharmacological activity of net fortnight at 50 milligrams in combination with impact of those net 10 milligram as measured by reductions in liver fat content by MRI P. D F N.
Enrollment is underway and eligible patients were randomized into one of four cohorts met four nine plus and back with closing net four nine alone and packet flows on alone or placebo.
The trial will enroll up to 120 patients in the U S and we anticipate assessing initial data and the first half of 2022.
In addition to net four nine development, we've recently initiated a phase Iia trial met 642 in patients with Nash.
While net ticks what she was derived from the same chemical family as met four nine and as such shares a number of the same properties met exports. You has two primary distinct pharmaceutical attributes first it is approximately 10 fold more potent which makes it more cost effective to produce and reduces the potential risk of off target effects and <unk>.
And were met or on nine has a mild to moderate Sip three four inhibition, we have engineered this out of metrics with you.
Late last year, we reported results from the completed phase one trial of metrics, where two and healthy volunteers demonstrating a sustained pharmacokinetic profile. After 14 days of daily oral dosing and robust FX, our target engagement as reflected by seaport suppression, which is a blood biomarker of bile acid synthesis that decreases with FX our activation.
In addition metrics what she was well tolerated with no observations of pruritus for LDL cholesterol increase at any dose level and no serious adverse events reported.
We are encouraged by the overall safety profile of metrics for two and with meaningful target engagement seen as low as the two five milligram dose level, we have proceeded into a phase II trial in patients with Nash evaluating three milligram and six milligram dose levels as each of these two doses are projected to suppress before to levels that are likely to result in meaningful reductions and.
Liver fat content.
This phase III trial of <unk> in Nash is currently enrolling patients. This is a 16 week randomized placebo controlled multicenter trial evaluating the safety Tolerability and pharmacological activity of met exports you as measured by levels of liver fat reduction by MRI PD effects.
The trial will enroll up to 180 patients and the U S and and interim analysis is plant and the fourth quarter of this year. After approximately 60 patients have completed 16 weeks of treatment followed by topline data expected from up to 180 patients and the first half of 2022.
Now based on the data generated with net fortnight and met six <unk>, we believe both FX our assets represent an important advancement and the treatment of Nash and we're very pleased that the FDA has granted net fortnight as well of metrics for two fast track designation, which underscores the agency's acknowledgment of the significant unmet need for treatments and patients with Nash.
We plan to take only one of these compounds forward in the Nash indication.
Advancing both net fortnight and metrics for tube through phase III development, we've given ourselves the greatest opportunity to select the optimal candidate based on the totality of data and their overall profile in patients with Nash.
We plan to assess the net fortnight monotherapy data and national we've already generated alongside the interim findings of metrics for two in the same patient population anticipated in the fourth quarter and then from this we intend to pick the compound that will progress into later stage development in Nash as a monotherapy and combination agent.
Importantly, we also believe that the learnings about the potential combination of ethics are agonism with <unk> two inhibition. That's gained from our ongoing study of met four nine combined with impact on closing may be applied to whichever epic's our candidate we advance for Nash.
Now while Nash is a major focus of the company today, we have enormous opportunity even beyond this one indication there are strong biological rationale for FX, our agonist development in other indications, including the large chronic indications of inflammatory bowel disease or IBD as well as orphan cold static diseases.
We plan to expand our development footprint into IBD and further evaluate the potential for orphan called static indications in 2022, and we look forward to discussing these plans and the upcoming months in.
In addition, our research and discovery team is actively investigating multiple novel non FX our programs in the liver and Gi space, which supports our approach to building a sustainable pipeline for the future.
So in summary, we've made remarkable progress and have a clear set of priorities for the next 24 months.
First priority is to rapidly bring our ethics, our agonist program to registration development for Nash, which involves assessing and clinical data from both net fortnight and metrics with you later this year and selecting a candidate of choice for late stage development.
Second priority is to expand the reach of our ethics, our agonist program leveraging its pipeline and a product potential beginning with IBD clinical trial work in 2022.
Given the size of the markets for both Nash and IBD, we plan to advance the same candidate for both indications. We then plan to evaluate our other ethics are agonist for one or more orphan liver cold static indications, which we'll talk more about in the future.
Third priority is to leverage our deep research and discovery capabilities to develop a portfolio of novel treatments for patients with liver and GI diseases. There are a number of compelling areas and our research team is exploring and we look forward to providing updates as we advance our discovery programs.
And fourth priority is maintaining a strong financial position and disciplined approach to capital allocation, our current cash and investments, including the funds raised through our IPO last fall fuel. Our currently planned operations through 2022.
And lastly, as we focus on these priorities, we will continue to foster company culture centered around effectiveness efficiency and enjoying it at the core of any good company is its people and we are committed to enabling a culture that empowers our employees to fly their individual talent and capabilities to further our corporate goals because there are patients and families who need the therapies that we are developing.
As we look ahead medica and has a significant opportunity for long term value creation with both and industry, leading <unk> platform and deep R&D capabilities to bring multiple first and best in class programs and patients.
By doing so we believe we can build a sustainable vibrant biopharmaceutical innovator for liver and Gi diseases and.
And with that we thank you for joining us today and we'll open the line for any questions operator.
Thank you and front of mind.
To ask a question you will need to press star one on your telephone so let's try a question press the pound key please standby will be compile the Q&A roster.
Our first question comes from Brian Abrahams with RBC capital markets. Your line is now open.
Oh, Hi, good morning, and congrats on all the continued progress thanks for taking my questions.
My first question is as you look towards the.
Potential a decision as to which candidate to move forward I guess.
What are your latest thoughts on like what the most important parameters are going to be coming out of the 642 study to compare it two to four O. Nine is it more about sort of PK PD and things like AUC and see for how important are the P. D. F. F results, how important will safety.
And drug drug interaction potential b, how do you sort of weigh all the different.
And different things that might come out of the study and what's what are the most important things and your view.
Sure Good morning, Bryan and thanks for the question.
So really great question.
<unk>.
Focus of examining our assets FX our assets is really.
To do that and Nash patients.
We can't do this from a preclinical perspective, or even and phase one and get really great information, but really in order to understand and be able to thread that needle in terms of the benefit risk profile, we believe it needs to be tested and Nash patients and so that's what we're doing and.
And so the other.
Characteristics that you mentioned.
Nearly a focus on pharmacological activity clinical activity in the form of liver fat reduction with MRI PFS is very important but also that safety and tolerability profile look mashes up is a chronic disease patients often don't have symptoms until later in the course of disease and so it's critical that that you have a therapy that.
Patients can take over a long period of time, and that's kind of and the accused heel for many of the other epics our programs and development in terms of things like brightest and and increases in LDL and so we're really focused on that and so from our perspective, what we've seen with four nine to date looks really great in Nash patients as a profile, we think it looks potentially class leading.
And we think that 642 can look as good as perhaps even better.
Some of the characteristics that we talked about.
A 10 fold greater potency.
And a few other of biopharmaceutical attributes that we think could potentially have demonstrated and even better profile than four O nine but just to be clear, we really like the profile of four and and I would think thats potentially class, leading and so when we look at the data.
600, <unk> that will get later this year it'll be about focus on pharmacological activity from them from a clinical perspective based on liver fat reduction as measured by MRI <unk>, and then really that safety and Tolerability profile. What are we seeing in terms of.
<unk> increases and LDL, what we've seen with 409 is very low single digit increases and LDL and very low incidence of mild to moderate price, where essentially nobody comes off drug as a result of that and if we can see that or potentially even better was 642. Then then that'll be a really nice set of assets to choose from in terms of picky.
And wanted to move forward into Nash and then for the compound and that does not move forward into Nash, we have the opportunity to think about orphan liver call a static conditions, where we fundamentally believe the ethics of our mechanism makes sense.
Got it that's really helpful and then.
There's been a number of developments and the clinical and regulatory side in Nash over the last six to 12 months, particularly amongst epic Sars and I guess I'm.
Yes.
And maybe some of the concepts coming out of the recent FDA workshop as well as some of some regulatory challenges that others have faced are shaping your latest view as to the safety bar and and the benefit risk profile that regulators might look for how that might guide your development strategy overall.
Yeah, another great question and.
And the overall our position is what we've heard from the FDA is that the bar has not changed there is clear guidance. It is based on an accelerated approval pathway.
Biopsy of course through the regulatory end point, and then and then and the post approval setting on the studies continue in terms of gathering information on clinical outcomes and we're encouraged by what the FDA has said repeatedly over the recent months related to their commitment to this accelerated approval pathway. We're also encouraged by the fact that for example, we received fast track designation for.
Both of our FX, our assets and that again underscore as you can see and recognition of the unmet need debt there is in that and.
And so we're essentially just focus on what the guidance is focused on demonstrating that we recognize that everything comes down to benefit risk balance and so that's why we're so focused.
On developing a differentiated profile with our ethics our assets. We believe that we've done that debt. We've got a potential class class, leading epic's our profile with net four nine and we think meant 642 looks fantastic in terms of phase one and has an opportunity to show up and the same way or even better.
And four nine and so it's really about developing a compound that you can that you can stand behind from a risk benefit perspective, we think the kind of guideposts are well laid out and we don't think that anything has changed fundamentally as a general rule in terms of what what agents what classes what mechanisms have to show in order to get approved and so we think we're on.
And a good place and we've just got to continue forward with with our progress and get into late stage development.
Great that's really helpful. Thanks, so much.
Thanks for the question.
And as a reminder to ask a question you will need to press star one on your telephone.
Our next question comes from Michael Yee with Jefferies. Your line is now open.
Hey, guys, Hey press and good morning, I had two questions. One was maybe just on the phase two study you could talk to the timing.
And pace of enrolment, how things are going.
And the timing of the Q4 interim announcement.
And I feel like that might've been changed for mid mid 'twenty. One should maybe just talk a little bit about that are you being conservative and how the process of that is going particularly during COVID-19 and then the second question.
Yes.
Remind us how youre thinking about plans and Gi or maybe that is also never orphaned cosmetic indications just in terms of whether you were still think about going into U C et cetera, and there's not the plan for the molecule that you don't take forward. Thank you.
Yeah, Yeah, great question.
So just in terms of our.
Our progress with the $6 two as well as frankly, four nine and the combination study that we're doing at four nine and the <unk> two inhibitor and packet flows and.
The short answer is that we are on track.
And of course, Covid has impacted the entire industry and a variety of ways, but to date, we have not seen a material disruption and our clinical development efforts and we're obviously being very vigilant pursuing all avenues to ensure that our programs do not have material delay and so.
We're providing more specific guidance as you always do overtime.
We don't view this as a shift.
And anyway and.
And and Hubert can speak to kind of additional.
Aspects of our operational programs that were making sure that we're very vigilant with related to COVID-19, and and moving forward and then I'll just say in terms of getting into inflammatory bowel disease with ulcerative colitis and the opportunities that we may have in terms of where from colas static conditions. Our first priority right now in terms of expanding beyond <unk>.
Nash is clearly our primary focus today, we're really excited about it.
Kind of the next wave in terms of expanding those indications is really a focus on inflammatory bowel disease that would be and ulcerative colitis and and proof of concept trial and those trials are typically 12 weeks and duration endoscopic findings in terms of primary endpoints headset.
Et cetera, and we'll talk about that more as we go.
Get closer to making that decision with respect to which asset we take forward into Nash score nine or six <unk>, which ever ask that we take forward into Nash. It makes sense that that's also the one that you test and inflammatory bowel disease because of the size of the patient population for these two chronic diseases. We will also then be evaluating opportunities for.
And the asset that does not move forward into Nash.
It can work in terms of orphan liver cause static conditions, we think theres opportunity. There we're looking into that further and that will be kind of the second wave of consideration after inflammatory bowel disease. We are definitely committed to moving forward and to a POC trial in ulcerative colitis patients for IBD here, where do you have any additional comments about the operational.
Yes.
Hey, Mike. Thanks for the question no I think pressed and cover it quite nicely. We're always vigilant in terms of the enrollment right. Now we are on track to deliver those messages and 42 results in the fourth quarter as we stated and mccrone I of course, and the first half of next year and of course, we will.
And our refined this guidance as we get more operational data, but right now that we've had the pleasure of visiting several of our investigators.
And what the proper Covid protocol and I will say that every site is fully engaged and Dudley GOP debt. They are working on optimized extra development candidates. So stay tuned, but we're quite encouraged by the progress we're making to date.
Thank you guys and person and that makes sense about the size of the population versus auction could you share the molecules.
Great. Thanks, Mike.
Thank you.
I'm showing any further questions at this time I would now like to turn the call back over to question caution for closing remarks.
Frivolous and thank you everyone for joining us on the call today. Thanks for the questions. We look forward and keeping you updated on our progress of course, and we hope that everyone stays safe and healthy have a great day, and we'll talk soon bye bye.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
[music].
And.
[music].
And then.
And.
Okay.
[music].
Okay.
[music].
And.
[music].
And.
And then.
[music].
Net.
[music].
And.
[music].
And.
[music].
Sure.
[music].