Q3 2022 Syros Pharmaceuticals Inc Earnings Call
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
[music].
Okay.
Good day and welcome to the Q3.
22, Syros Pharmaceuticals, Inc earnings Conference call.
At this time all participants are in a listen only mode.
After the speaker's presentation, there will be a question and answer session to ask a question. During the session you will need to press star one one on your telephone you will then hear an automated message advising that your hand is rate. Please.
Please be advised that today's conference is being recorded I would now like to turn the conference over to your Speaker Ms. Karen.
Director of corporate Communications and Investor Relations. Please go ahead.
Thank you.
This morning, we issued a press release announcing our third quarter 2022 financial results and a broader business update.
The release is available on the Investor and media section of the cirrhosis website at Www Dot com.
We will begin the call with prepared remarks by Dr. Nancy Simonian, our Chief Executive Officer.
Dr. David Roth, our Chief Medical Officer and.
Jason Hart, our chief financial.
<unk> officer, we.
We will then open the call for questions Kristen, Steven our Chief Development Officer Dr.
Dr. Eric Olson, our Chief Scientific officer.
Kindly Qi, our chief commercial officer are also on the call and will be available for Q&A.
Before we begin I would like to remind everyone that the statements. We make on this conference call will include forward looking statements.
Actual events or results could differ materially from those expressed or implied by any forward looking statements. As a result of various risks uncertainties and other factors, including those set forth in the risk factors section of our annual report on Form 10-K, and our quarterly report on.
On Form 10-Q that we filed this morning and any other filings that we may make with the SEC in the future.
Any forward looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date specific.
Specifically disclaim any obligation to update or revise any forward looking statements I would now like to turn the call over to Nancy.
Thank you Karen.
Morning, everyone and thank you for joining us today.
The third quarter was transformative for steel.
In September we announced the concurrent close of our merger with time technologies and are oversubscribed.
Nancy.
Together these transactions netted approximately $190 million provided.
Providing us the necessary cash to continue ended up gain in the clinical development of our late stage targeted hematology programs. While also supporting initial launch readiness.
Our goal has always been to build <unk> into a commercial company.
With this additional capital we believe we are in an important step closer to achieving this foundational vision and ultimately to delivering our portfolio of medicines to people living with cancer.
Now I'll turn to the initial data we announced this morning from the safety lead in portion of our ongoing phase one trial evaluating on slide 56 or not.
As David will review shortly these data provide further evidence that CDK <unk> inhibition is a potentially important therapeutic approach for treating pancreatic cancer one of the most devastating and difficult to treat malignancy.
As well as other difficult to treat tumor types.
We're encouraged by $56 nine emerging safety profile, both as a single and combination agent.
And by the clinical activity, we've observed in pancreatic cancer with several patients achieving stable disease, and one patient achieving a confirmed partial remission.
We reached a maximum tolerated dose as a single agent or in combination.
And given the emerging exposure response relationship plan to continue dose escalation with both single agent and $56.
And then the doublet combination with Gemcitabine.
At the same time, we've always said that data from this phase one trial evaluated in the context of our own strategic priorities will inform the best course for further development of this program.
While we believe there is a strong rationale to advance 50 609 in pancreatic cancer as well as in other difficult to treat solid tumors.
We believe this will be best done in the hands of a partner who has the resources to maximize the opportunity both in pancreatic cancer as well as additional combination regimens and tumor types.
To that end, we plan to explore partnership opportunities, while we continue to dose escalate.
We look forward to providing an update at the appropriate time in the future.
Importantly, we are excited to continue to support Roche is ongoing arm evaluating 50 609 in combination with <unk> in patients with BRAF mutant colorectal cancer in their phase one wouldn't be intrinsic trial.
Turning to our hematology portfolio as you know <unk> is our selective and potent oral <unk> alpha agonist, which has the potential to offer a new standard of care to be approximately 50% of Mds and 30% of AML patients who are paused.
<unk> four <unk> over expression.
We are currently evaluating <unk> in two clinical trials.
Mds 180.
Pivotal phase III trial in higher risk Mds patients.
And select AML, one if phase II trial in newly diagnosed unfit AML patients.
As we announced in our press release last week, we will be we'll be sharing initial data from the safety lead in portion of the select AML one trial at the Ash annual meeting in early December .
We are highly encouraged by the initial clinical activity observed in the study to date.
We initiated both the select MBS, one and select AML one trials based on the belief that <unk> in combination with type of less leading agents alone.
With <unk> has the potential to improve clinical outcomes for Mds and AML patients with Barbara overexpression.
We previously reported phase two data with <unk> in newly diagnosed unfit AML patients with Robert over expression, which showed a high CR cri rate with a rapid onset of action.
And now we are excited by the early data from select one trial, which together with the data from our prior phase two trial support the potential for <unk> to augment existing standard of care and meaningfully improve outcomes for both AML and higher risk.
Mds patients.
We look forward to presenting updated data from the select one trial at Ash and request that you save any questions on data from our trial until our presentation on December 10.
Looking ahead, we continue to expect data from the pivotal select Mds one trial in late 2023, or early 2024 and to initiate the randomized portion of the select AML, one phase II trial with data expected in 2023 or 2024.
In addition, we are making good progress in our ongoing dose confirmation trial of FY 'twenty 101, our novel oral form arsenic trioxide or bto for the treatment of frontline patients with acute myeloid leukemia or APL.
We are on track to identify the optimal dose to advance into our planned phase III trial, which we expect to initiate in the second half of next year.
And as we announced on our Q2 call based on feedback from both the FDA and EMA. We believe we will be able to use a single registration trial to support the approval of 20 <unk> hundred one in both the United States and Europe .
We are excited by the potential of each of our product candidates and confident in our ability to execute with excellence.
Each of our ongoing clinical studies.
And we are grateful for the support of our new and existing investors, which we believe will enable us to bring forward. These new medicines that redefine the standard of care for patients with difficult to treat tumors.
We look forward to our upcoming catalyst and continuing to work towards our mission of making a profound difference in patients' lives.
I would now like to turn the call over to David.
David.
Thank you Nancy.
Today, I will focus my discussion on slide 56 or <unk>.
Earlier. This morning, we announced initial safety data as well as early clinical activity data from the safety lead in portion of our ongoing phase one trial of $56 nine which is evaluating our highly selective and potent oral CDK <unk> inhibitor in combination with chemotherapy.
In patients with relapsed refractory pancreatic cancer.
We also provided updated data from the ongoing single agent portion of the trial in advanced solid tumor patients.
I think we had a cancer is one of the most devastating in difficult to treat malignancies.
Today, the only approved agent for second line pancreatic cancer is uninvited and combination with five <unk> and Luca born which offers a median progression free survival of approximately three months.
In September we received orphan drug designation from the U S FDA.
609 for the treatment of pancreatic cancer.
Underscoring our urgency to develop 56, Illinois for pancreatic patients, whose tumors have otherwise you alluded therapeutic intervention.
As a reminder.
Phase one trial is evaluating 50 609 in combination with chemotherapy and pancreatic cancer patients who progressed following treatment with <unk>.
Patients are being enrolled to receive either <unk> 56 in combination with gem side of being first or second relapse.
50, 609 in combination with Gemcitabine and Nab Paclitaxel in first relapse.
Move to doses of the combination agents.
The study is assessing safety and tolerability as well as efficacy measures such as disease control rate and progression free survival.
As Nancy mentioned earlier were encouraged by the data we shared today.
First on characterizing the safety and Tolerability of <unk> 56 or nine.
As a single agent.
And in combination with chemotherapy.
We're very pleased to report that as.
I also have an October 12 cutoff 50, 609 was observed to be generally safe with enhanced tolerability being maintained in the seven day on seven day off regimen.
Highest doses tested.
To date, we've evaluated 56% up to 10 milligrams when administered as a single agent.
Up to five milligrams when administered in combination with Gemcitabine.
And up to 40 milligrams when administered with both Gemcitabine and Nab Paclitaxel.
This underscores the importance of our careful dose optimization strategy that resulted in our development of an intermittent dosing regimen that allowed for promising advances in our ongoing trial.
Describe now.
The single agent 10 milligram dose did not result in any further.
Further supporting a tolerability of seven day on seven days off regimen, which has now been evaluated 30 patients across five dose levels ranging from four to 10 milligrams with only one DLT observed at the four milligram single agent dose level.
Across all arms of the study and MTV has not yet been reached seven day on seven day off regimen.
The adverse event profile of $56 nine in combination with chemotherapy was consistent with the safety profile of single agent <unk> $5600.
Or gemcitabine mono therapy, or Gemcitabine and Nab paclitaxel.
And the majority of adverse events were low grade and reversible with no new safety signals identified.
The most common related adverse events in the cohort with $56 nine and Gemcitabine.
We're the highest 56 doses were evaluated in combination with chemotherapy.
Fatigue.
Russia decreased appetite and decreased platelet count.
Great.
One patient experiencing a DLP of grade three diarrhea at the five milligram <unk> dose level.
No <unk> were reported in patients treated with 50 609 in combination with Gemcitabine and Nab Paclitaxel.
Turning now to clinical activity.
As of October 20th data cut.
Two of three enrolled patients in the 10 milligram single agent cohort, we're responsive valuable, including one patient with pancreatic cancer and colorectal cancer.
Both patients achieved stable disease, and notably the patients with pancreatic cancer also experienced a 10% tumor reduction.
In the cohort evaluating the doublet combination of 5600, <unk> and Gemcitabine in patients with pancreatic cancer.
<unk>, 425% of response Evaluable patients treated at the four milligram <unk> dose level experienced a confirmed partial response or PR with a 98% reduction in the CA 19, nine tumor marker from our baseline of 60350.
Seven units per milliliter nine.
968 minutes.
Which is impressive considering this patient was not responses to prior treatment with frontline full fair enough.
Three or four or 75% of response evaluable patients treated at the five milligram 156, <unk> dose level had stable disease for an overall disease control rate of 50%.
Importantly data from the doublet and 10 milligram single agent dose cohorts support and emerging exposure response relationship to.
The patient from the doublet, who achieved a confirmed PR demonstrated higher than average exposure relative to other patients at that dose level.
And the cohort evaluating the triplet combination of $56 nine and Gemcitabine and Nab paclitaxel in pediatric patients.
One of two response evaluable patients treated at the four milligram dose level achieved stable disease.
Based on these Taylor and as Nancy mentioned earlier, we plan to continue dose escalation of $56 nine to 15 milligrams as a single agent and to 10 milligrams in the Gemcitabine combination cohort in hopes of leveraging the emerging exposure response relationship to enhance <unk>.
<unk> activity with higher doses.
And to better characterize the therapeutic index.
In parallel we will explore partnership opportunities to advance 50, 692 patients, allowing us to devote our resources to our late stage hematology programs.
As Nancy alluded to earlier, we're making tremendous progress across our hematology portfolio, where we are advancing tami Barron team and FY 'twenty 101, as a potential standard of care therapies for the <unk>.
Online treatment of Mds, AML and APL.
We look forward to presenting our initial select ammo one data at ash in December and to sharing additional details with you there.
I would now like to turn the call over to Jason to review, our third quarter financial results Jason.
Jason.
Thank you David we continue to operate from a position of financial strength in September we closed our merger with time technologies through which we acquired time, including its pipeline assets and net cash of approximately $68 million.
Currently we closed our previously announced oversubscribed type financing through which we raised $130 million.
The pipe was led by life Sciences focused investment funds and included new and existing <unk> shareholders, such as flagship pioneering avidity partners deep track capital Bain capital Life Sciences.
In this same Sara.
Ally Bridge and Cowen healthcare investments.
These transactions together with the amendment to our senior secured loan facility with Oxford finance significantly extended our cash runway.
We ended the third quarter with approximately $245 million in cash and cash equivalents, which we believe will be sufficient to fund our planned operating expenses and capital expenditure requirements into 2025, approximately a year past our expected pivotal data readout for select Mds one.
Now turning to our third quarter financial results, we recognized $3 $9 million in revenue in the third quarter of 2022.
Consisting of $3 $7 million from the collaboration with GBT and $200000 from our collaboration with insight.
For the third quarter of 2021, we recognized $5 $7 million of revenue under our collaborations with GBT and insight.
R&D expenses were $25 8 million in the third quarter of 2022 compared to $27 3 million for the third quarter of 2021.
This decrease was primarily attributable to a decrease in external costs associated with our preclinical programs.
G&A expenses were $8 $1 million in the third quarter of 2022 compared to $5 3 million for the third quarter of 2021.
This increase was primarily attributable to an increase in employee related expenses and an increase in recruiting fees.
Transaction related expenses were $9 5 million in the third quarter of 2022. These expenses principally relates to the pipe financing, which are allocated to warrants classified liabilities and severance paid to former <unk> employees.
We reported a net loss for the third quarter of $30 3 million or $3 21 per share compared to a net loss of $26 million or $4 14 per share for the same period in 2021.
Finally, following the 10 to one reverse stock split, which we implemented in September as well as the close of the merger and pipe transactions. We ended the quarter with approximately 28 million shares of common stock and pre funded warrants to purchase common stock.
This includes 22 million shares of common stock and $7 5 million pre funded warrants with that I will turn the call over to the operator for questions.
Thank you.
As a reminder to ask a question you will need to press star one one on your telephone please standby, while we compile the Q&A roster.
My first question.
It will come from the line.
Edward <unk> with Piper Sandler. Please go ahead.
Hey, guys. Thanks, so much for the update and congrats on all the progress really looking forward to the data at a hematology just wanted to see if you can kind of give us a little bit more of a expectation of what to what we should expect there. Thanks.
All right. Thanks, Ted So we're very excited about the upcoming ash presentation and.
We're looking forward to presenting updated data at that time.
Right now were.
Planning to take further questions about that at the meeting when we will be able to dig in and give you a lot more color and context around what's presentation has to show.
Great and I think as we said in the press release expectations are to initiate the phase III portion.
When could that happen.
Yes.
Hey, Todd.
Thank you cut out, but I think your question was around the.
<unk> faced the randomized portion.
Yes.
Provided to provide at ash on up.
Date on kind of the next steps with the trial.
Great. Thank you for the thing in New Orleans.
Great. Thanks, Pat.
Thank you as a reminder, if you would like to ask a question.
Please press the star one one.
Our next question will come from the line of Philip Nadeau with Cowen. Please go ahead.
Good morning, what does that our congratulations on the progress a couple of questions on $56 nine to start you mentioned that you hope to better define the therapeutic index for <unk> 56 or nine can.
Can you give us some sense.
With the monotherapy and combination arms what.
Response rate or does the disease control rate do you hope to see to give you confidence that there is efficacy over background.
And this population once you do hit an MTBE.
Sure. Thanks, Phil for that for that question. So.
As you can gather we're very excited about the data that we've generated which we have just shared with you.
We've already demonstrated in the doublet with 56 nine plus gemcitabine.
At relatively low doses of <unk> 56 to nine mind, you that we have in aggregate to disease control rate of about 50%.
With four out of the eight patients having disease control, which is CR plus PR plus stable disease. So we feel that that's a very very exciting at this early stage in particular, because that is clearly in line with other benchmarks for combination therapies in this type of population with pancreatic cancer.
Now the other comment I would make is our emerging data have clearly to us demonstrated what we are referring to is an emerging.
The exposure response relationship.
Where we're able to show with the single agent that when we increase the dose of the drug we get a proportional increase in the <unk>.
Okay waiting levels of the drug in blood and that's very exciting because that gives us reason to believe that more drug will give you more.
More exposure.
And we saw a similar phenomenon even in the doublet, where the patient who was dosed with four milligrams of 66, nine plus Gemcitabine standard doses 1000 milligrams.
Had a durable confirmed resist partial response.
With a dramatic reduction in the tumor marker CA 1990 went from over 60000 down to below 1000, I mean that was really significant so.
So the notion that we havent seen.
Any maximum tolerated dose yet.
Of the regimens with the $7 seven off.
Schedule and we can push the dose even further gives us reason to hope that.
It may be better with respect to the clinical activity, which we think could provide a really meaningful impact for patients with pancreatic cancer.
So I hope that sort of answers your question, but in aggregate, we find the data quite compelling.
That does help and then maybe a question on the partnership can you give us some sense of in your mind, who would be the ideal partner and then kind of Conversely.
If no one signs on would you start a phase II trial on your own.
The partnership discussions continue.
So I mean, we're going to be looking at a variety of strategic partnership opportunities for $56 nine thank.
<unk> heard from David we're very excited about.
Clinical activity that we're seeing the tolerability, including in combination the emerging exposure response relationship and we think that selected the CDK <unk> inhibition.
That opportunity in a broad range of tumor, it's a really big opportunity. So we're.
Excited about the opportunity to speak to folks about.
Partnering to take the drug forward, we think that's sort of in the best interest of maximizing the value for the program, while we focus our resources on our targeted hematology portfolio at this point in time we.
We're going to continue to dose escalate, but right now no plans for further moving beyond the safety lead in portion of the trial.
That's very helpful. And then last question I know you don't want to discuss more about the data or the plans forward for slipping one can.
Can you remind us according to the design was the hurdle for the safety lead in portion.
Moving on to the randomized portion was there a specific.
Safety profile of that had to be achieved.
So I think.
In general the safety lead in is designed to make sure that you have sort of a dosing schedule that you are comfortable moving forward with into the randomized portion.
Obviously also we're looking at clinical activity as well and as you know the some of the doublets of Tami ASR and then Asia.
In a similar patient population have come.
Composite CR rates in kind of low to mid 60% range. So clearly we're also looking for the opportunity to have something higher than that as we think about moving into the next phase of the trial and we're excited about the.
The initial data that we have and we look forward to discussing that at ash.
That's very helpful. Thanks for taking our questions.
Thank you one moment for our next question.
And that will come from the line of Alexander Sue with Oppenheimer. Please go ahead.
Hi, This is Alex calling on behalf of Mark at Oppenheimer.
Got a few questions first off with the CDK Kevin programmer.
We noticed.
Like 56 are not using combination therapy.
What was the logic behind not continuing the testing importantly, 50 679 plus.
Axel.
The AAA.
Sure.
Thanks, Alex.
That question so.
We are again very excited about the data we're seeing across all of the arms, where we have not yet demonstrated a maximum tolerated dose.
And I do want to just remind you we've dosed up to 10 milligrams in a single agent up to five in the gym doublet and up to four and in the.
Jim.
Our triplet.
Obviously, it's very important to focus on the single agent arm to define a maximum tolerated dose. That's that's really a critical in general and drug drug development because it helps to define our ceiling for dosing and I think that clearly has a research priority and then it's very.
Straightforward to understand the contribution of 56% owing to the activity of Gemcitabine. When you add the two together you can clearly interpret the doublet on the backbone of that single agent. So those have garnered our interest with priority for next steps.
That said, we also feel that it's important to help to define the doublet because it's on the basis of the doublet that will interpret the outcomes of the triplet. So the doublet enables the triplet to move forward.
And we haven't explicitly said, we're not going to.
Retained interest in the triplet at some point in the future, but we think the next immediate steps should really just focus on on those too.
There'll be foundational for moving to.
<unk> program forward.
No.
Great. Thank you.
Mike My next couple questions. So I have a question about your annual program.
So we retro abstract and we noticed that one of the.
Poor responders discontinued treatment due to physician decision.
Do you mind elaborating on kind of what the factors contributing to this decision.
Yes, as we said earlier, we're looking forward to presenting data at Ash and we're all kind of discuss details of the data at that time.
Okay No worries, thanks, Steve Yes.
Thank you.
I'm showing no further questions in the queue at this time I would now like to turn the call back over to Nancy Simonian for any closing remarks.
Thank you operator, and thank you everyone for joining us today and for your continued support of <unk>. The remainder of 2022 will be an exciting period and we look forward to updating you again soon please reach out with any further questions have a great day.
This concludes today's conference call. Thank you for participating you may now disconnect.
Yeah.
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
[music].
Okay.
Okay.
[music].
Good.
Okay.
[music].
Okay.
Okay.
Yes.
Yes.
Okay.
[music].
Sure.
[music].
Yes.
Yes.
[music].
Okay.
So.
Dan.
Yes.
Thank you.