Q4 2022 Syros Pharmaceuticals Inc Earnings Call
Speaker 1: So.
Speaker 1: The.
Speaker 1: And.
Speaker 2: Good morning and welcome to Seros from a Siricol's fourth quarter and full year 2022 financial results conference call. At this time, all participants are in listed animal. This call is the webcast live on the investors and media section of Seros website at www.seros.com. Please the advice that today's call is being recorded.
Speaker 2: At this time I would like to turn the call over to Keren Hunari, Director of Industrial Relations and Corporate Communications at CIRE.
Speaker 3: Thank you. This morning we issued a press release announcing our fourth quarter and full year 2022 financial results. The full release is available on the investors and media section of the Syros website at www.syros.com. We will begin the call with prepared remarks by Dr. Nancy Simone.
Speaker 3: and kindly cheat our Chief Commercial Officer or 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 may differ materially from those expressed or implied by any forward-looking statements as a result of various risks.
Speaker 3: uncertainties and other factors, including those set forth in the risk factors section of our annual report on Form 10K 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.
Speaker 3: marked a meaningful year for Syros, in which we made important advances towards our pursuit to deliver new standards of care for the frontline treatment of hematologic malignancies.
Speaker 3: Today, we are focused on our late-stage programs in MDF, AML, and APL, three diseases in which there is significant need for more convenient and well-calorated treatment options that improve clinical outcomes while still maintaining patient's quality of life.
Speaker 3: We believe that MDS, AML, and APL markets are attractive with business synergies that we plan to address through our own commercial efforts in the U.S. Over the past year, we reached important milestones in our HEEM programs. In December , we announced positive data from the safety lead-in portion of the MDS, AML, and APL.
Speaker 3: of the Select AML1 study, enabling us to move into the randomized portion of our Phase 2 study this quarter.
Speaker 3: In August , we announced promising preliminary data from our Doath confirmation study of S.Y. 2101, which, if additional data are supportive, we believe could enable an efficient go-to-market strategy.
Speaker 3: We continued progressing the ongoing select MDS-1 Pivotal trial, and in recent months, we've seen momentum in side activations and enrollment across our global sites. And in January , we were delighted to receive FDA fast-track designation for Tammy Baratine for the treatment of higher risk MDS, underscoring the critical need for new treatment options for this patient population.
Speaker 3: We are now in the second quarter of 2025 with a successful close of our September 2022 financing in which we secured approximately 190 million in capital.
Speaker 3: Importantly, we believe these proceeds are sufficient to fund our cash requirements past phase three data from the Select MDS-1 trial and data from the randomized portion of the Select AML-1 trial, while also allowing us to begin investing in pre-commercial activities important in bringing our therapies to market. Together, these accomplishments provide a tremendous foundation.
Speaker 3: as we look ahead and prepare for a multiple upcoming catalyst. Specifically, we expect to complete enrollment in the Select MDS-1 Phase III trial in the fourth quarter of 2023 and to announce pivotal data in the third quarter of 2024. Share initial data from the randomized portion of the Select AML-1 trial in the fourth quarter of 2023 followed by additional data in 2024.
Speaker 3: and share an update on the dose confirmation study of 2101 in APO and next steps on a registration pathway in the second half of 2023. I would now like to turn the call over to David to provide a more detailed update on our ongoing clinical programs. David? Thank you Nancy. Today I'll provide an update on our clinical stage pipeline and walk through the upcoming readouts we anticipate over the next 18 months.
Speaker 2: First, I'll begin with tummy baritone in MDS. As Nancy mentioned, we're pleased by the FDA's recent decision to grant fast-track designation to tummy baritone for the treatment of higher risk MDS, allowing us the opportunity to potentially expedite the delivery of tummy baritone as a new standard of care for people living with this progressive disease. As we've discussed before, today, newly diagnosed higher risk MDS patients have limited available treatment options.
Speaker 2: The existing standard of care, hypo-methylating agents, offer only a 17% complete response rate and a median survival of 18.6 months. And no new therapies beyond HMAs have been approved since 2006.
Speaker 2: The FDA grants fast track designation to help speed the approval of new drugs for which non-clinical or clinical data demonstrate the potential to address a significant unmet medical need. Therapeutic candidates that receive fast track designation may be eligible for more frequent interactions with the agency.
Speaker 2: as well as priority review and accelerated approval if supported by clinical data. In recent discussions, the FDA has reiterated its support for our face redesign, including using complete response rate as an appropriate endpoint for regulatory decision making, along with supporting data on durability of remission. We continue to see steady progress in our pivotal select MDS-1 trial.
Speaker 2: The only actively recruiting registration enabling trial in front line higher risk MDS that we are aware of. We now have over 90 sites activated in 13 countries and we are encouraged by physician enthusiasm at the open clinical sites. We continue to expect to complete enrollment in the fourth quarter of this year and look forward to sharing pivotal CR data in the third quarter of 2024. Now, turning to our study of Tammy Baratine in unfit AML or the approximately half of AML patients.
Speaker 2: who are not eligible for intensive chemotherapy due to their age or an underlying medical condition. Today, the standard of care for unfit AML patients is the netaclacks with ASIS-I-DT or Venesa, which has shown a 37% CR rate and a median overall survival of 14.7 months. Unfortunately, approximately one-third of patients do not respond to frontline Venesa, and nearly all relapse. And when these patients relapse, they have a very poor prognosis with median overall survival rates of only 2.4 months. At ASIS in December , we announced positive data from the Safety Lead-In portion of our Select AML1 study. The triplet combination of Tammy Baratine and Venesa.
Speaker 2: In newly diagnosed unfit AML patients with RARA overexpression, demonstrated an 83% CR-CRI rate with rapid onset of action.
Speaker 2: The data also showed that Tammy Baratine in combination with approved doses of Venn and Asa showed no evidence of increased toxicity relative to historical data with the doublet combination of Venasa in this population. This includes rates of mylo suppression.
Speaker 2: So based on these data, we moved into the randomized portion of the Select ML1 study, which we initiated in the first quarter of this year. The randomized portion of the trial is designed to evaluate the safety and efficacy of Tammy Baratine in combination with Venasa compared to Venasa.
Speaker 2: In approximately 80 newly diagnosed unfit AML patients with RARA overexpression who are randomized 1-1 with composite CR-8 as the primary endpoint. We look forward to announcing initial data from the randomized portion of the trial in the fourth quarter of 2023 and additional data in 2024. Lastly, I will turn to 2101, our novel oral form of arsenic trioxide or ATO. Which is currently being evaluated in an ongoing dose confirmation study for the frontline treatment of APL.
Speaker 2: Approximately 2,000 people are diagnosed with APL in the US and EU annually, and the current standard of care is IVATO combined with oral atro. While effective, IVATO is very burdensome for the patient, involving up to 140 treatment infusions, each over 2 to 4 hours for nearly a year.
Speaker 2: We believe an oral ATO therapy could significantly reduce this treatment burden while also increasing access and reducing health care costs and utilization. We believe 2101 could provide exactly this offering patients an all oral regimen that is both effective and allows for a better quality of life.
Speaker 2: We believe an oral ATO therapy could significantly reduce this treatment burden while also increasing access and reducing health care costs and utilization. We believe 2101 could provide exactly this offering patients an all oral regimen that is both effective and allows for a better quality of life. We're making good progress in the dose confirmation study.
Speaker 2: As Nancy mentioned, in August , we announced initial data from the trial demonstrating high oral biodevailability of approximately 80% with exposures comparable to IVATO based on both CMACs and AUC. Based on these emerging data, we believe there may be an opportunity to explore a more efficient registration pathway to potential approval. We plan to share an update on the dose confirmation study and next steps on a registration pathway in the second half of this year. In all programs, we continue to make excellent progress across our hematology pipeline.
Speaker 2: We're advancing three programs through late-stage development, each with the potential to become standard of care and to dramatically improve the lives of patients. We have multiple catalysts upcoming this year and next and look forward to providing additional updates soon. I would now like to turn the call over to Jason to review our fourth quarter and full year 2022 financial results. Jason?
Speaker 4: Thank you, David. Now I'll turn to our fourth quarter and full year 2022 financial results. As Nancy mentioned, we extended our collaboration agreement with Global Blood Therapy Dix this past December for another year. As a result, we extended the amortization period of the upfront payment that GBT made to us at the start of the agreement in 2019. This required us to make a one-time cumulative catch-up adjustment to true up the revenues recognized in the fourth quarter.
Speaker 4: Therefore, we recognized negative $800,000 of revenue from the GBT collaboration in the fourth quarter. For 2023, we will continue to recognize the revenue from GBT as we have in the past. For the full year, we recognized $14.9 million in revenue, consisting of $13.6 million under our collaboration with GBT and $1.3 million under our collaboration with Insight. For the fourth quarter of 2021 and full year 21, we recognized a total of $7.8 million and $23.5 million of revenue, respectively from our collaborations with GBT and Insight. R&D expenses were $27.9 million in the fourth quarter and $111.9 million for the full year. As compared to $26.8 million for the fourth quarter of 2021, we recognized $1.2 million in revenue from GBT and $1.3 million in revenue.
Speaker 4: and 99.9 million for the full year 2021. Both the increases for the fourth quarter of 2022 and full year 2022 were primarily due to increased costs associated with the continued advancement of our clinical programs and employee related expenses.
Speaker 4: Based on our current operating plans, we expect that our future R&D expenses relating to our preclinical and drug discovery stage programs will be reimbursed by our collaboration GNA expenses were $7.3 million in the fourth quarter of 2022 and $29.3 million for the full year 2022 as compared to $6.4 million for the fourth quarter of 2021.
Speaker 4: and 23 million for the full year 2021. Transaction-related expenses of $9.5 million for this past year primarily consisted of incurred costs allocated to the warrants issued in connection with the pipe financing that were accounted for as liabilities and severance paid to former time employees following our acquisition of time, which closed in September 2022. We reported a net loss for the fourth quarter of $4.8 million or $17 per share compared to a net loss of $23.8 million or $3.78 per share for the same period in 2021.
Speaker 4: For the full year ended December 31, 2022, Syrus reported a net loss of $94.7 million or $7.49 per share compared to a net loss of $86.6 million or $13.84 per share for the same period in 2021. Cash equivalents and marketable securities as of December 31, 2022 were $202.3 million as compared with $143.4 million at the end of 2021. We believe our current cash position will be sufficient to fund our interests.
Speaker 5: please press start, followed by the number one. If you want to withdraw your question, please press start, do.
Speaker 2: Your questions will be pulled in the other day. Chief, sorry, should you please hit the handset before pressing Yankees. One moment please for your first question. Your first question comes from Phil Nadu from TV Dandra. Please go ahead. Hi, good morning. Thanks for taking our questions. A couple of from us. First, on the data from Select AML1 in Q4, can you talk a little bit more about the quality of data that you'll be able to release at that time, approximately how many patients with how much follow up and...
Speaker 2: what endpoints do you think you'll be willing to disclose? Great, so I'm going to ask David to take this. Sure, thank you Phil. So, you know, as we've just reported, we've initiated enrollment into the randomized portion of the trial and we anticipate reporting data coming out of the randomized portion of the study. We haven't yet specified the total number of patients that would be available. Keep in mind it'll be balanced randomization, one to one into each of the two arms. So we look forward to getting insights into the performance of the triplet combination versus the doublet in patients who have rar over expressions. It can be very important to provide us with context as to how to interpret the data. And, you know, as usual, we'll report on the response rates and available other information, you know, durability and any available safety to help.
Speaker 2: continue to understand how the triplet is working. So I think we should all look forward to that data presentation as an important update. That's helpful. And then second on 2101, could you maybe share with us some possible designs of a more efficient registration path to approval? What type of efficiencies do you think you could realize after you have discussions with the FDA? So the answer is no. We haven't yet disclosed specific alternative design options. So it's premature for me to comment on that. But I mean, I do think it's fair for me to give you some insights into that. As we initially designed that study, which we vetted with the global regulatory agencies, we had really important and encouraging data.
Speaker 2: came coming out of Orsonics, which demonstrated the exposure relative to historical data with IV arsenic. And we are really the first to ever test directly in patients, the oral versus IV, and to provide properly collected data that could support a PK evaluation to really hone in on the exposures and the appropriate dosing. That's what this has been all about. It's a dose confirmation study. And so we as you know we previously shared you know later last year, earlier last year that is that we have data emerging that really supports encouraging outcomes both based on CMACs and AUC and high bioavailability that really supports you know new ways of thinking about how to streamline the development strategy. And you know I guess streamline could mean fewer patients or...
Speaker 2: shorter times to delivering the data. And that's what we're all about is bringing this forward as quickly as possible. So without specifically giving you great details, I think you could look forward to that update in the second half of the year, and you'll have more insights into how we're thinking about things. That's helpful. Thanks again for taking our questions. Thanks, Bill. Thank you. Your next question goes from my rising deck from OpenHinder. Please do ahead. Hey, good morning. Thanks for taking our questions. Just a couple of quick ones for me as well. First of all, can you just remind us if there are any futility analyses built into this Select MDS 1 protocol that we could see between now and toppling data in the third quarter of next year?
Speaker 4: And then the second question is just housekeeping for Jason. I'm wondering if Share Count has stabilized now. I think it's around $20.3 million in the 10K. Is that number expected to fluctuate much or as kind of settled around there following the merger with time? Thanks for taking the questions. Hey, Marick, I'll take the first one. So on the futility, we have not guided to any expectations for futility analysis. So I think really the focus should be on the pivotal CR data in the third quarter of 2024. Okay. And Mark, it's Jason. On the Share Count, we have $20.3 million basic shares outstanding, and that ought to remain relatively stable. We also have $7.5 million pre-funded warrants. So the way I would think about our Share Count.
Speaker 6: And then for 201, have you already had interactions with FDA that support the potential for next up expedited path or if not, can you talk about what plans you would have to interact with FDA before we get the update later this year?
Speaker 3: So I'll have David take the first and just to clarify the second question was ready to make the between 21 and 1 th and was that we were to
Speaker 2: There would be any, okay, yeah. So with respect to the AML, you're asking about whether the AML trial is stratified by multiple? What is selecting based on any selection based on the monocytic phenotype? Yeah, no, so we were not. The criteria are consistent with the design of the original phase two, if the newly diagnosed unfit.
Speaker 2: provided they have raw overexpression using the same test we've used all along. Obviously, we are going to be collecting that data and looking at that, and that's going to be very important for us to understand that correlation. We did report from the ash presentation. You may recall we had six.
Speaker 2: patients who were valuable for clinical activity, and we saw an 83% CRCRI rate, which was really encouraging. And of five of the patients at that time who we had the monocytic expression score evaluated for were positive. So, you know, that's again, 80% positivity rate, which was spot on for the prior analysis from the phase two. So we have reason to predict consistency of data across the trials, and you know, look forward to giving you an update.