Q3 2022 Fulcrum Therapeutics Inc Earnings Call
These may include statements about our future expectations and plans clinical development timelines and financial projections.
While these forward looking statements represent our views as of today, they should not be relied upon as representing our views in the future.
May I take these statements in the future, but we are not taking on an obligation to do so please refer to our most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with our business.
With me on today's call are Bryan Stuart President and Chief Executive Officer, and Aster Roger value, our CFO , Paul Bruno our senior Vice President of corporate development will also be available for Q&A.
Now let me quickly run through this morning's agenda, Brian will begin the call with a corporate overview and key updates including on our clinical programs.
Joe will cover our financial and Brian will open the call for Q&A with that it's my pleasure to turn the call over to Brian .
Thanks, Stephanie and good morning, everyone and thanks for joining us today.
At Fulcrum, our mission is to treat the root cause of genetically defined rare diseases and this quarter. We have continued to make progress towards bringing transformative therapies to patients.
Currently we have two clinical programs with the potential to dramatically transform the treatment paradigm in sickle cell disease and F. S. H D.
We are committed to moving both programs through the development and regulatory process as rapidly as possible to address the significant unmet needs that we know exist in these patient populations.
We are also continuing to invest in our research engine and expect to file our next <unk> in 2023.
Yes.
At our last update we announced a strategic realignment to prioritize our internal investments in our two key value driving clinical programs intended for the treatment of Fsh D. N S. C D.
This extended our runway into mid 2024 at that time.
In August we closed an underwritten public offering that resulted in net proceeds of approximately $81 million that has extended our runway further and we are in a strong cash position that enables us to continue to execute on our mission.
<unk> will provide details on our financials later in the call.
Moving on to our clinical programs, starting with our phase <unk> sickle cell disease program.
S. T D is a debilitating disease that for far too long has lacked effective and tolerable treatment options.
Hbf induction is the only mechanism, which has been shown to broadly improve outcomes and reduce both the frequency and severity of SPD symptoms such as V O sees anemia pain fatigue and acute chest syndrome.
That's the X 60, 58 is an H b F inducing agent that has the potential to address the unmet need in sickle cell disease <unk>.
Including symptoms not addressed by current therapies.
Several independent lines of evidence, including human genetics, and emerging gene editing data support our therapeutic goal that are 5% to 10% increase in H B S above baseline can reduce both mortality and morbidity associated with S. T D.
An oral therapy that can produce robust increases in H B O S.
Been a therapeutic goal in sickle cell disease for some time, which is why the initial data from our F. T X 60, 58, one b trial are so exciting.
We have shown compelling proof of concept that SPX 60, 50, a rapidly induces H b S protein in sickle cell disease patients and demonstrated that it is able to achieve absolute H b S increases within the range that clinicians have targeted for a potential future standard of care.
As our work on the phase one B trial continues we will continue to focus on understanding the effect of 60 58 across multiple dose dose cohorts and the consistency in response to a 60 58, both as monotherapy and in combination with Hydroxyurea.
In addition to our ongoing six milligram and two milligram dose cohorts, we have selected 12 milligrams.
As the dose for our next cohort and plan to continue enrollment into 2023.
Our goal is to have high quality data across multiple cohorts to inform our plans for our registration enabling trial in 2023.
Yes.
We have been focused on clinical trial operations and trial conduct during the second half of the year. We have increased the number of sites that are participating in the program and have targeted our recruitment efforts in areas with meaningful population of people living with sickle cell disease.
We are focused on building connections and partnerships with the SCD community because we understand that local community based organizations have been on the front lines of the fight to treat sickle cell disease.
The feedback that we've received from the community has been clear the accessibility and ease of use of a new SCD therapy is extremely important.
Our approach of developing an oral small molecule that can be taken once a day and deliver robust hbf induction has been met with very positive response from patients and health care providers.
Now moving onto our F. S. H D program, where we are currently enrolling the phase III reach trial.
Reach was designed as a highly efficient 48 week trial is intended to be registration, enabling both in the U S and ex U S geographies.
We continue to be well positioned to bring our first to market therapy for this relentless and devastating disease that is the second most common form of muscular dystrophy.
People with F. S. H D lose strength function independence, and mobility as a disease advances seeing their quality of life decline as a result.
There is an urgent need for disease modifying therapy that can help patients with S. S. H D maintain their quality of life.
Data from our phase III <unk> four trial indicates that road map them on has the potential to slow or stop disease progression and in some cases, even improve function in F. S. H D patients.
In October at the World Muscle Society meeting in Halifax, Nova Scotia, We shared 96 week data from our open label extension trial in the ongoing phase two b redux for.
Over 97% of patients and the initial 48 week trial decided to remain in this study during the open label extension.
Top line results showed that participants in the initial treatment arm, who continue to receive less mathematic demonstrated maintenance of effect through a 96 week period as measured by change and reachable workspace or our ws from baseline.
Notably those who crossed over from placebo to lowest map a month. After the initial 48 week trial period demonstrated slowed disease progression based on the same measures.
Well its a mathematic also continued to maintain its favorable safety profile and was generally safe and well tolerated.
We have strong conviction in this program and our interactions with patients and the clinical community continue to reinforce the potential for those map them out to become the standard of care for F. S. H D.
We expect to complete enrollment for the phase III trial in 2023.
As we continue to make progress on our two lead programs. We are very excited to welcome two additions to our executive leadership team.
Dr. Santiago Arroyo joint broker him yesterday, as our Chief Medical Officer, Dr. Roy always a neurologist by training with two decades of experience in drug development.
He most recently served as the Chief Medical officer of momentum Pharmaceuticals through its acquisition by Johnson and Johnson we.
We have great confidence in Doctor of ROI of his experience and leadership and are incredibly pleased to have him at the helm of our clinical organization as we look towards having two registration enabling trials in 2023.
We have also appointed Doctor Doctor, Jeff Jacobs as our Chief Scientific Officer, Dr. Jacobs has more than 25 years of experience in drug discovery and has led coed and meant toward multiple discovery programs from concept stage to IND, enabling studies.
Dr. Jacobs, who was most recently the chief Scientific officer, Goldfinch, bio and will be joining fulcrum as of December 1st we are thrilled to have both onboard to lead our efforts towards filing our next <unk> D. In 2023.
With that I will hand, the call over to Aster to review, our third quarter financial results.
Thank you Brian .
As Brian mentioned in the third quarter, we strengthened our balance sheet and cash position with our equity offering in August .
We announced an underwritten public offering of approximately 11.
The common stock at an offering price of $7.82 per share.
The gross proceeds from this offering were approximately 85 million before the deduction of underwriting discounts and other offering expenses and resulted in net proceeds of $81 million to the company.
This offering in addition to the strategic realignment plan that we announced during our second quarter call.
Naval sauce to operate our business from a position of financial strength.
And to remain focused on executing on our key value driving pathway.
Now turning to the third quarter financials.
During the third quarter of 2000 2010 collaboration revenue was $1 2 million compared to $4 9 million during the third quarter of 2021.
Oh I see.
Third quarter 2022, operating expenses remained relatively stable at 25, and a half million compared to $25 7 million for the third quarter of 2021.
R&D expenses were $15 4 million for the third quarter of 2022 as compared to $17 1 million for the third quarter of 'twenty one.
G&A expenses were $9 7 million for the third quarter of 22 compared to 8.6 million for the third quarter of 2021.
Our net loss for the third quarter of 'twenty, two with $23 7 million compared to a net loss of $20 7 million for the third quarter of 2021.
We ended the third quarter with a cash cash equivalents and marketable securities balance of 221.8 million.
Based on our current operating plans, we expect that our cash will be sufficient to fund our operating expenses and capex requirements into late 2024.
We are operating from a position of financial strength and remain disciplined about deploying capital appropriately to our key value driving.
With that I'll turn it back to Brian .
Thank you Esther.
This third quarter for Fulcrum was focused on execution and we've been able to make major strides in both of our lead programs.
As we move into the fourth quarter with a new clinical and scientific leadership team, we are well positioned to establish fulcrum as a leading rare disease company, we advanced two potentially life changing therapies and continue to leverage our research engine to expand our pipeline all supported by a strong financial Foundation.
And with that I'll turn it back to the operator for questions.
Yeah.
Thank you.
We will now begin the question and answer session.
To ask a question you May Press Star then one on your Touchtone phone.
If youre using a speakerphone please pick up your handset before pressing the keys.
If at any time. Your question has been addressed and you would like to withdraw your question. Please press Star then two.
At this time, well pause momentarily to assemble our roster.
Yeah.
Okay.
The first question comes with.
Matthew Harrison with Morgan Stanley . Please go ahead.
Yes.
Hi, Thanks for taking my questions Theres, just one John on LIFO, Matthew So I have two questions one about dosing and what about the trial execution of the 60 58 program. So in terms of the dosing, what's the rationale to choose 12 Mg and <unk>.
These joe's, saying say about what you have seen.
<unk> two combo with Hydroxyurea and the second question is how is the trial executed so far.
Even.
You mentioned continuing enrollment into 2023, which is kind of delay from the previous guidance of year end 2022, and what is your plans for data disclosure off the trial. Thank you.
Great Yeah. Thank you for the question, let me start with the rationale on dosing and then I'll I'll speak to trial execution, and let our aster speak to data disclosure so and in terms of rationale I think one of the things is as we mentioned and maybe we'll start off with our therapeutic goal.
For the program has always been to see increases in H B F of the 5% to 10% above baseline knowing that all of the Ah.
Human genetic data the emerging gene editing data all of that points to this being a transformative therapy with a small molecule once daily if we can achieve that we were excited by what we saw at the six milligram dose as we shared at Ehealth. Realizing that that was an early dataset and we wanted to generate more data.
As we.
And at that time, we wanted to get experience with both monotherapy and in combination with <unk> at both the six and two milligram dose. We are actively doing that and that gives us the comfort based on the PK PD modeling that we've done as well as the data that has been emerging from section two.
To move towards the 12 milligram dose and the plan is at the 12 milligram dose just like the other dose cohorts to get data, both monotherapy and in combination with Hydroxyurea.
In terms of trial execution.
This has been a big focus of the company one of the things that we mentioned are at Ehealth is that we were transitioning towards observed dosing. We are now utilizing that I think what we can say is we are.
Believe it is effective.
And our goal from a trial execution perspective, as we spoken to is less about quantity of data and number of patients, but more about high quality data, making sure that we are generating good data.
From Ah patients that are adherent that will really help inform our next trial with our goal of that being a registrational trial. So I think that is proceeding well we are going to be continuing enrollment into 2023 and that will be focused on all three dose cohorts and we believe that that is going to be able to.
To provide sufficient data to transition into that Registrational trial, I'll, let aster speak to disclosure yeah.
I think with regards to the data disclosure will have more information for you in the first quarter.
Okay. Thanks.
Okay.
Yeah.
Thank you.
The next question comes with taken Hot with people. Please go ahead.
Great. Good morning, Thanks for taking our questions and congrats on all the progress. So maybe a question on 60 58, and then another follow up for $6 58, if we look back at the Phase II <unk> study if I'm looking at a correct are they had about 12 sites GBP four four O study at about one <unk>.
Out in the U K, you've got about seven right now that I'm seeing I know, it's a dated October so what are you actually sharing from boots on the ground with regard to rate of enrollment and aside from the U N C site that you've recently added I think it was in September .
Guess, what additional strategy can you implement to expedite enrollment to make it more of a one half 'twenty three complete enrollment rather than a second half and then a follow up I guess would be when we look at the trial couldn't trials entry in September you updated it so that it now adds up to three additional cohorts.
And and has been increased to 40 versus 20 previously I guess any insight you can provide in terms of what we can look forward to beyond the 12 milligram cohort. Thanks, so much.
Thanks, Dave.
Maybe I'll first speak to the changes that we made to accommodate additional cohorts and then I'll turn it over to Paul and he can talk about some of our efforts in enrollment and recruitment.
In terms of the additional cohorts.
As we mentioned at that time, we don't we don't have current plans to go beyond the three dose cohorts. However, we did want to provide the flexibility to potentially do so based on the data that we see so at this point our plan is to make the six Meg and the 12 milligram dose cohorts.
But should the data.
Lead us in a direction, where we think it would be helpful to dose additional cohorts, we've allowed ourselves the flexibility to do that.
And I'll turn it over to Paul to speak about enrollment.
Thanks, Brian .
Yeah, just with regards to our two enrollment again are our priority right now is enrolling a high number of high quality patients as opposed to focusing purely on quantity.
We think opening additional sites you know beyond a single site simply gives us the flexibility to make sure that we're enrolling the highest quality patients in this initial phase <unk> study.
Yeah.
Yeah.
Okay.
Okay.
Yeah.
Yeah.
Operator can we move to the next question. Please.
Sure. Thank you I'm sorry.
The next question comes with.
Judah Frommer with credit Suisse. Please go ahead.
Hey, good morning, guys. Thanks for taking the question just circling back on on the 12 big dose selection.
Can you give us an idea of how that.
Impacted are informed by the two Megan and six Mig phase <unk> data that you're seeing versus the the healthy data that you presented that went up to 10 and maybe the relationship that you're seeing on PK P D unhealthy versus patients.
Okay.
Yeah, good morning Judah.
Yeah. So as you referenced and I think we spoke about a little bit of that.
We wanted to get experience at six milligram cohort and the two milligram cohort with H U and in mono therapy prior to dosing hire we now have that experience. We now have the comfort to be able to dose up to the 12 milligram cohort and obviously, we're very excited to do so one of the things.
That will want to understand as we've spoken about is when we looked at our healthy volunteer data, we saw relatively robust target engagement across all doses, but there was a difference in mrna that we saw at the different dose levels. So that's something that we're going to want to understand better as we look at this 12 milligram data.
Not only to understand obviously safety and Tolerability, but to also see if there are differences in protein induction at the different levels and again, starting off with the base of a lot of excitement and enthusiasm that we have with the hbf increases that we shared it at <unk>. So that's how we were.
Thinking about it.
Okay, and then just on timing of a decision.
And the ability to dose higher your new CMO and C. S. So do they have any input into the 12 member that was kind of in place. When you started conversations with them and how do you see them kind of impact on the program going forward.
Okay.
Yeah. So we did make this decision along with both I think we can just say our internal team as well as external advisers in a DMC are obviously I think most importantly, particularly on the on the clinical side, we're thrilled to have Santiago joining.
He has tremendous experience in rare disease drug development at momentum at Pfizer are having led a number of very significant programs. So his experience jeffs experience on the preclinical side I think puts us in a tremendous position and obviously as you can tell I don't think we could be more excited about having both of them joined the organization.
Great Congrats.
Greater chemo can the next question please.
Yeah.
Sure. The next question comes with Matt Biegler with Oppenheimer. Please go ahead.
Hey, guys. Thanks for taking our question just wondering if youre in a position yet to see whether the efforts to improve on patient noncompliance are bearing fruit and if you could just kind of remind us again, what those efforts are in and if you're in a position yet to talk about what's working and what's not working.
I think any color would be great. Thanks.
Yeah, Hi, Matt. Thanks for the question and just as a reminder to everybody as you're referencing one of the things that we shared at <unk> is that we were transitioning to observe dosing and observe dosing is commonly used in a lot of small molecule drug development programs.
<unk> tends to be very effective.
<unk> put that in place at that time, and I think what we can say at this point is that yes, we do believe it's been effective.
This element of the trial has been a big focus of ours internally.
And we're we're pleased that as we've implemented this we do believe that it's working.
Thanks Kristina.
Next question please.
Next question comes with.
Joseph.
Fourth with SC SDB Leerink I'm sorry. Please go ahead.
Oh, hi, thanks, so much and congrats on the progress I was wondering if you can give us any insight into.
Where you are in enrollment with cohort two do you think.
Cohort two enrollment.
Could also stretch into 2023 or is it just cohort three and how many patients are you hoping to.
Generate data on in combination with H U versus monotherapy and then I have a follow up please.
Yeah. Good morning, Joe Yeah, Thanks for the questions.
So I think at this point and we are actively enrolling.
In both the two in the 60 milligram cohort we've been pleased with the progress that we're making both as monotherapy and in combination with <unk> I.
I think one of the things that we've been talking about and we've emphasized today. It really is this focus on quality data and that's going to drive our decision, making so as we get more data both monotherapy and <unk>, we want to really understand the variability and I think if obviously if there is greater variability.
We'll have a desire for more patients if there's less variability in the data I think that will allow us to proceed more quickly. So we're really going to make a data driven decision.
I think we can say as we sit here at this point to be able to be moving forward with three dose cohorts monotherapy and in combination we feel like that's going to put us in a very strong position to generate the data set that will allow us to transition into a phase three trial.
Okay.
Yeah, yeah. Thanks, so much. So I was wondering if you could give us any sense of whether you see any impact from.
From the video monitoring on enrollment it seems like that would certainly help.
Enforce compliance, but I just didn't know if.
In this space, where it's already fairly difficult to find patients to participate if that was.
Serving as any headwind now that you've implemented that.
On enrollment.
Yeah, and I think Joe what we can say at this point is we believe it's been effective.
Implemented this as we mentioned this is used broadly across the field and a number of different programs. I think were pleased with the results. We think it's been effective and we will continue to utilize it.
In terms of headwinds we don't believe so this is not something that is E invasive by any means.
So it's something that we can execute on I think patients have been more than happy to participate in it and it's going to allow us to generate the highest quality dataset and most importantly, the best data to make the right dosing decisions moving forward.
Okay, great. Thanks for all the helpful color.
Yeah. Thanks, Joe.
Thank you. This concludes the Q&A session for today.
I'd like now to turn the call over to Bryan Stuart for closing remarks.
Great. Thank you thanks, everyone for joining us and we very much appreciate the support of fulcrum have a great day.
Yeah.
This conference has now concluded. Thank you for attending today's presentation. Thank you all for joining us today and for your support.
Right.
Okay.
Okay.
Okay.
Yeah.