Q4 2022 Gracell Biotechnologies Inc Earnings Call
Speaker 1: The.
Speaker 1: The.
Speaker 2: I would now like to turn the call over to Dr. Kevin Chee, CFO . Please go ahead.
Speaker 2: Good morning and welcome to Graycell fourth quarter 2022 corporate update conference call on the webcast. Thank you for joining us today.
Speaker 2: With me today are Chris's founder and chief executive officer, Dr. William Tao, and our chief medical officer, Dr. Wean Andy.
Speaker 2: We're excited to discuss the progress of our differentiated clinical pipeline of CAR T therapies on today's call. We also look forward to sharing with you our recent business developments and upcoming objectives as we head into 2023.
Speaker 2: As our formal remarks, we will conduct a question and answer session.
Speaker 2: This morning, Griswold issued a press release announcing unaudited financial results for the quarter and the full year ended December 34, 2022. We encourage everyone to read this press release and would like to remind you that this call is being recorded for replay.
Speaker 2: Please note that for certain information discussed on the call today, including financial data, clinical data, and future plans of our program, resource management will be making forward-looking statements. Actual results could differ materially from those stated or implied by those forward-looking statements.
Speaker 2: as a result of various important factors.
Speaker 2: and please refer to the Risk Factors section of our latest 20-hour filing with SEC for a full disclosure of these risks and the factors.
Speaker 2: This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast.
Speaker 2: This conference call contains time-sensitive information that's accurate only as of the date of this live broadcast, March 13, 2023.
Speaker 2: The retail undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the date of this conference call, except as may be required by equitable securities law.
Speaker 2: I will now turn the call over to Grace of CEO , Dr. William Chao. William.
Speaker 2: Thank you, Kevin. And again, welcome everyone to our fourth quarter 2022 corporate update conference call.
Speaker 3: It has been a very productive few months for us.
Speaker 3: I will begin today's call with key pipeline updates.
Speaker 3: I will then turn the call over to our CMO, Dr. Wendy Lee, to provide insight into the two companies sponsored trials for GC012F in relapse refractory multiple myeloma that we plan to commence in 2023. Thereafter, our CFO , Dr. Kevin Xie, will...
Speaker 3: commercial potential of our lead autologous CAR T candidate, DC012F, in hematology and potentially immunology indications.
Speaker 3: Autologous catheterotherapy has now established itself as the most potent treatment for several hematologic malignant disease.
Speaker 3: But significant unmet needs continue to exist for patients and physicians.
Speaker 3: who are facing supply limits, long wait time, and high cost, as well as calling for improved safety and durable efficacy.
Speaker 3: These needs have been propelling the cartier industry to move forward and innovate.
Speaker 3: As Graycell would believe, 12F represents a next generation of autologous CUTI therapy candidates.
Speaker 3: and has the potential to push the boundary of autologous kai chi on many fronts.
Speaker 3: such as manufacturing speed, safety, cost, and even durability of advocacy.
Speaker 3: Utilizing our proprietary fast car manufacturing process.
Speaker 3: GC012F is comprised of younger, more fit T cells that are manufactured within 24 to 36 hours.
Speaker 3: Fast Cut not only helps to shorten patient wait time to weeks from months, but also provides key advantages.
Speaker 3: in advanced cell quality and cost saving.
Speaker 4: Next.
Speaker 3: Software features novel BCMA and CD19 dual targeting.
Speaker 3: This is designed to enable the deepest response and durable efficacy based on the dual mechanism of action.
Speaker 3: Our clinical data generated from 45 multiple myeloma patients has shown a consistent 100% MID negative rate in all patients treated with GC012F, which represents the deepest level of eliminating malignant cells in bone marrow.
Speaker 3: And on the durability side, we plan to provide an important data update from our relapse to refractory multiple myeloma investigator initiated trial study around midyear.
Speaker 3: And hopefully that it will add to the expanding body of evidence supporting 12F's significant potential.
Speaker 3: I also hope to point out that the dual targeting mechanism of action provides GC012F with wide applicability across diseases.
Speaker 3: where either BCMA or end CD19 could be ending targets.
Speaker 3: including multiple myeloma, NHL, and beyond, for example, in certain immunology indications.
Speaker 3: Lastly, but very importantly, GC012F has demonstrated a highly differentiated safety profile in IIT studies. If you are studying
Speaker 3: No neurotoxicity was observed in the 48 patients dosed in three studies underway in RRMM, newly diagnosed high-risk multiple myeloma, and in relapsed refractory non-hydric lymphoma.
Speaker 3: While the cytokine release syndrome, or CIS, observed in the studies has been mostly low-grade, it is also worthwhile highlighting that the median onset of CIS is around 6 days across our MM studies.
Speaker 3: These safety features could potentially provide critical differentiation and benefits in earlier lines or outpatient settings.
Speaker 3: Last month, we have announced that US FDA and China MMPA cleared our R&D applications.
Speaker 3: which included our China IAT data.
Speaker 3: Graycell has reached a very exciting juncture in its development life cycle as two company-sponsored studies evaluating 12-epine RMM are on track to commence soon.
Speaker 3: Advancing our lead FSCAR-T candidate towards a US-based 1B slash 2 clinical trial is a major milestone and we plan to initiate enrollment in the second quarter.
Speaker 3: The Phase 1-2 clinical trial in China is expected to commence in the third quarter of 2023.
Speaker 3: Our CMO, Dr. Li, will provide additional details shortly. In addition, we remain very excited about the data we have gathered so far in our IT studies. We have been under way to evaluate GC012F in a newly diagnosed
Speaker 3: high-risk multiple myeloma patients. The first inpatient data from this trial was presented at an oral session of the ASH Annual Meeting in December 2022.
Speaker 3: We were overwhelmed by the very positive reception from the medical community on the data. SKOLs are optimistic about our candidates' potential in frontline settings.
Speaker 3: We continue to follow up this study and anticipate sharing additional data later this year.
Speaker 3: As a reminder, we also unveiled the first data from an ongoing IIT of GC 012 in relapsed refractory NHL at IHA in June 2022. We are continuing the enrollment in the follow-up.
Speaker 3: of these patients in ongoing study and plan to share the updated data at a medical meeting in 2023.
Speaker 3: Moving on to the off-the-shelf True UCAH platform, DC502 is our True UCAH-enabled CD19-CD7 dual-directed allogeneic CAR T therapy candidate being evaluated as a treatment for RRBALL.
Speaker 3: At last year's EHOP, we presented updated IIT data, which shows three out of four treated patients achieved MID- negative CRI. This study is ongoing. Next, moving on to our donor-derived CAR T.olina D.
Speaker 3: In October , we announced the dosing of the first patient in China, registration of phase two trial evaluating GC double seven G in an allogenetic CD19 targeted conscious cell therapy!
Speaker 3: Double 7G is derived from HLA-matched donor for the treatment of RRB-ALL patients who fail to transplant and may not be eligible for autolivous CAR T therapy.
Speaker 3: We have observed highly encouraging safety and efficacy data in the Phase 1 portion, and we hope to share the data later 2023.
Speaker 3: Lastly, SmartCART is our second generation technology for the treatment of solid tumors and utilizing a novel construct to take advantage of the suppressive tumor microenvironment and effectively combat solid tumors.
Speaker 3: Preparations are underway for an IIT trial for the second SmartConT candidate.
Speaker 3: DC506 targeting quality 18.2 and enrollment is on track to commence in the coming months.
Speaker 3: As we're heading to 2023, we're very optimistic about continued advancement of our highly differentiated Kati platform as we are on track to commence two company-sponsored trials.
Speaker 3: Advanced enrollment in ongoing studies.
Speaker 3: and push forward other initiatives.
Speaker 3: We look forward to providing several clinical data updates at upcoming medical meetings throughout 2023.
Speaker 3: Now, I will hand the call over to our CMO, Dr. Wendy Lee, to discuss our participation at ASH in December .
Speaker 3: Wendy, please go ahead.
Speaker 5: Thank you, William. In the U.S., we plan to initiate a company-sponsored phase 1b and 2 clinical trial evaluating GC012F for the treatment of relapsed and refractory multiple myeloma.
Speaker 5: during the second quarter of 2023. We received clearance from the U.S. FDA for IND application in January 2023.
Speaker 5: The phase 1B portion of the trial is designed to evaluate the safety and the tolerability of DC012F into those levers and to determine
Speaker 5: The recombinant phase two dose.
Speaker 5: of therapy in the fist 1B portion at two dose levels.
Speaker 5: We plan to activate up to five to ten slides.
Speaker 5: that are very experienced in conducting CAR T-12.
Speaker 5: We currently anticipate completing the phase 1 portion during the first quarter of 2024 and then holding an end of phase 1 meeting with FDA shortly thereafter in 2024 to align on the next steps.
Speaker 5: Turning to the company's sponsored trial in China, we plan to initiate elements in the FIF 1 and 2,12, evolvating GC 012F in RRMM during the third quarter of 2023.
Speaker 5: The fifth one portion of the trial is designed to evaluate the safety and tolerability of TC012F across two dose levels and to determine the RPTD.
Speaker 5: We plan to enroll approximately nine patients at one clinical site in China and anticipate completing enrollment in the phase one portion during the first half of 2024. Last December , the children were labeled fordate households with Walter minirophic infections after doing five hard cases late in documented decay.
Speaker 5: and oral presentation on the first clinical data from ongoing IIT evaluating GC012F.
Speaker 5: A newly diagnosed multiple myeloma patients was conducted at the ARSH annual meeting.
Speaker 5: The data demonstrated that GC012F achieved 100% overall response rate and 100% MRV activity in all 16 transplant eligible high-risk NDMM patients.
Speaker 5: across all those levers.
Speaker 5: The safety profile was excellent as 75% of the treated patients did not experience any cytokine release syndrome. Also, no e-mail effector cell associated neurotoxicity syndrome.
Speaker 5: or other neurotoxicity of any grid has been observed. We have received significant enthusiasm from the medical community since the ASH presentation.
Speaker 5: As the data highlighted an impressive 100% ORR and 100% MRD negative in first line patients,
Speaker 5: that have multiple high-risk features and regardless of whether they have responded to the short induction therapy of two rounds of RVD before the infusion of GG012F. In contrast,
Speaker 5: The current standard of care for newly diagnosed multiple myeloma usually includes as many as four to eight rounds of induction therapy, which can be triplet such as RVD or
Speaker 5: quadruplets such as the direct TMMF plus RVD, followed by autologous stem cell transplant, and then a few years of maintenance therapy.
Speaker 5: At the end of the transplant, SCR is typically 30% to 40%. An MRD negative rate could be between 20% to 40%.
Speaker 5: of the transplant, SCR is typically 30% to 40%. An MRD negative rate could be between 20% to 50%.
Speaker 5: It's also worthwhile to mention that typically with the standard of care, it can take a year or more between diagnosis and completing the transplant.
Speaker 5: While with CAR T.
Speaker 5: The median time from diagnosis to infusion of GC012F in the ongoing trial was less than five months. So, our data is among the first to demonstrate the material benefits CAR T can bring to the newly diagnosed
Speaker 5: multiple myeloma patients.
Speaker 5: including shortening the diagnosis to treatment time.
Speaker 5: deepening the response and maximizing the response rate.
Speaker 5: All achieved with a good safety profile.
Speaker 5: We continue to follow the patients in our study to further evaluate the long-term benefits.
Speaker 5: We are very encouraged by this initial data and currently evaluating the path
Speaker 5: forward for this indication. I will now hand the call over to our Seattle Dr. Kevin Xie. Review
Speaker 2: Thank you, Wendy. Turning to our financials, I'd like to touch on a few financial trends.
Speaker 2: As of December 31, 2022, the company had RMB 1,458.2 million for US dollar 211.4 million in cash and the cash equivalents and the short term investments.
Speaker 2: We expect the cash used for this year to be approximately $100 million.
Speaker 2: primarily to fund our R&D and clinical programs in the US and China.
Speaker 2: We expect our current cash provision to be sufficient to cover our operation plan and R&D activities towards the end of 2024.
Speaker 2: My loss attributable to ordinary shareholders for the three months ended December 31, 2022 with RMB $130.7 million for US dollar 18.9 million.
Speaker 2: compared to RMB 128.6 million for the same period in 2021.
Speaker 2: My loss attributable to ordinary shareholders for the full year ended December 31, 2022 was RMB 607.5 million or US dollar 88.1 million.
Speaker 2: compared to RMB, 453.7 minutes for the same period in 2021.
Speaker 2: Research on the development expenses for the three months ended December 31, 2022, with RMB 113.1 million for U.S. dollar 16.4 million. As compared to RMB, 107.6 million.
Speaker 2: for the same period in 2021. The full year ended December 31, 2022. Research and the development expenses were RMB 485.4 minutes or US $70.4 minutes.
Speaker 2: compared to RMB, 326.9 million for the same period in 2021.
Speaker 2: Increases were primarily due to the increased spending on research development and the clinical itself as well as higher paid-all and the personnel expenses.
Speaker 2: attributable to increased headcounts and a higher facility related costs in support of continued expansion of research and development activities. With that, I'd like to turn it back to the operator to open the session for your questions.
Speaker 2: to increase headcount and a higher facility related costs in support of continued expansion of research and development activities. With that, I'd like to turn it back to the operator to open the session for your questions. Operator?
Speaker 6: The floor is now open for your questions. To ask a question at this time, please press star 1 on your telephone keypad. If at any point you'd like to withdraw from the queue, please press star 1 again. You will be provided the opportunity to ask one question and one further follow-up question. We'll now take a moment to render our roster. Our first question is for you, Mr. Chairman.
Speaker 6: and the line of Yigal Neshabat from Citi. Please proceed.
Speaker 5: Hi team, this is Carly on Korea Gal. Thanks so much for taking our questions.
Speaker 5: First, can you comment on the vein to vein time you are anticipating for GC012F in the US phase 1 with the current process and quality control procedures that you have in place? And then I guess how much further do you believe that can be optimized as you move into later stage development and How much further do you believe that can be optimized as you move into later stage development and quality control procedures that you have in place? And then I guess how much further do you believe that can be optimized as you move into later stage development and
Speaker 3: eventually the commercial setting. Hi, Carly. Very good question. The first part is very good. The second part is better.
Speaker 3: the commercial setting? Hi, Carly. Very good question. The first part is very good. The second part is better.
Speaker 3: Let me sort of put together pieces so that you understand, you know, because each other, we're probably using different definitions. So let's say delivery time, meaning we receive the sample and return the cells to the hospital.
Speaker 3: That's supposed to be seven days. However, you add on logistics and then QC everything. It's about 12 days now.
Speaker 3: That is supposed to be seven days. However, you add on logistics and QC everything. It is about 12 days. Now,
Speaker 3: Before I get to link for depletion, OK? The release in tests in our hand is five days, seven days.
Speaker 3: However, we in the US
Speaker 3: the test is being done by third-party laboratory. So that will add on a few more days.
Speaker 3: So it's not going to be seven days of reading tests. It's been probably nine days, 10 days, and perhaps even longer. So that part I can't give you a definitive answer yet.
Speaker 3: So basically it's three days manufacture from receiving and by having the belt ready plus
Speaker 3: week to seven or some days to ten days of testing days. Now
Speaker 3: Rain to rain time.
Speaker 3: including liver depletion. So that will add on three days plus.
Speaker 3: So total together I would say about probably up to three weeks.
Speaker 3: The second part of the question is,
Speaker 3: Is there any possibility to optimize? Yes, of course. Moving forward, we will establish in-house quote, quote, the test can be done within CDMO. Then it will shorten the time of logistics shipping in and out.
Speaker 5: Okay, great. That's super helpful. And then we just had one follow up. I guess we've heard from some companies that are rolling – No, sorry. Connie. Oh, yeah. Connie, there is one more – one minor point I would like to add on here. Oh, sure. Sure. If we could further optimize –
Speaker 3: the releasing test, let's say shortened from seven days to five days, for example, then here is some area we can optimize as well. Okay, perfect. And then our follow-up was just on enrollment. I guess we've heard from some companies that...
Speaker 5: enrolling late-line myeloma patients in the US is becoming increasingly difficult given the availability of the BCMA by specifics. So just curious any feedback you're hearing from KOLs around this and what steps you could take to facilitate enrollment in the Phase I, too. Thank you so much.
Speaker 4: Sure.
Speaker 3: Wendy, do you want to meet?
Speaker 5: try first and then you can... Yeah, go ahead. Yeah, go ahead. My signal is not very good. Please, bye-bye.
Speaker 3: That's what we hear is slightly different. Perhaps the PIs, the carriers we have been working with are very enthusiastic and seems to us that Phase 1B is a very important part of the process.
Speaker 3: 12 patients in Roman, not going to be an issue.
Speaker 3: Now, hopefully, you know, our sites, we select our very experienced that we know, and hopefully, the patient, experience, the other ones, if not all, is that it collected information
Speaker 3: enrolling in that site and also looking forward to fast delivery products like GC 012m. Anyhow, so far we don't have any special concern about the speed of enrollment.
Speaker 3: Does that answer your question? Or Wendy, do you have anything to add on?
Speaker 4: You're right, you're also perfect.
Speaker 3: Thanks, Kati. Did we answer your question?
Speaker 6: Our next question comes from the line of James Shin from Wells Fargo. Please proceed.
Speaker 2: Good morning guys, thanks for taking my question. I just wanted to touch base on
Speaker 7: comments regarding a partnership and it didn't seem quite, it didn't seem mentioned in the press release and then I have a follow up.
Speaker 3: Yeah, you haven't seen the press release. You're right. I would wish, you know, you come to material.
Speaker 3: Since our ASH presentation of newly diagnosed multiple myeloma study and the immediate news about IND filing, we do receive positive response and interest.
Speaker 3: But I can review more details, you know, in that direction.
Speaker 3: But please be ensured that's top of our priority. This is the right way to go. So we'll continue to pursue that. Got it, okay. And then for the quadrant program,
Speaker 3: that's top of our priority. This is the right way to go, so we'll continue to pursue that. Got it. Okay. And then for the quadrant program, what sort of...
Speaker 7: Would you expect to see responses this earlier? Is this sort of like a proof of concept? Can you say anything on your expectations for a solid two minutes for cell therapy? The turnaround time program.
Speaker 7: you expect to see responses this earlier? Is this sort of like a proof of concept? Can you say anything on your expectations for solitude meters for cell therapy? masses radiation millennium!
Speaker 3: Yes, GC 506. Okay, yeah, the target is Claudia 18.2.
Speaker 3: We will initiate clinical IT first, which will commence very soon, I believe. Yeah, very soon. So we'll have.
Speaker 3: in a reasonable time to assess solid tumor response. But this will take, I don't know, six months to evaluate.
Speaker 3: to assess body tumor response. But this will take, I don't know, six months to evaluate the new product.
Speaker 3: Okay. All right. Thank you. Yeah. Right. We haven't published any data including credit.
Speaker 3: the clinical data mechanism studies so I can't really comment on the details but the purpose of this whole program or the objective of the new design on Claudia 18.2 plus the smart device is to enhance the efficacy and we believe
Speaker 3: with other tumor, you do need a strong push of the CAR T-cell into tumor tissue to combat the suppressive environment.
Speaker 3: So hopefully with additional smart design plus this widely recognized target 18.2, we're going to see some big enough.
Speaker 3: Hopefully with additional smart design, plus this widely recognized target 18.2, we're going to see some signal. Bye.
Speaker 3: this MOD design plus this widely recognized target 18.2, we're going to see some signals. But we didn't have to wait.
Speaker 7: Thank you for that. Our next question comes from the line of Justin Zellin from BTIG. Please proceed. Hi, good morning, guys. Thanks for taking the question and congrats on the progress here. I had a question just on the IIT durability data that we're expecting later this year.
Speaker 7: Are you targeting a medical meeting for disclosure of that data or could that come as kind of a company event here? And I have a follow-up. It's going to come out in part of July .
Speaker 3: Yeah, Wendy, I think that's for you.
Speaker 5: Yeah, that's right. Yeah, we're going to have to explore the data later this year for the meeting or the managed craft. So yeah, we're, we're looking forward to popping those information.
Yeah, that's right. Yeah, we're going to explore the data later this year for the meetings or the managed craft. So yeah, we're looking forward to popping this information later.
Right, yeah, we're going to explore the data later this year for the meetings or the managed craft. So, yeah, we're looking forward to public those information later, but we think this year.
Okay, great. May I add on? You hear from Dr. Lee that both paper and presentation conference plans, so whichever come out first.
It's possible, end of the year, if you ask for any EIADs, we can get in on time. And if the paper published earlier than that. So it's all ballpark. We'll end this here.
Got it. Okay, that makes sense to me. And then for the 29 patients, I think the last update we got last year, the median duration of follow-up was approaching a year. For this next update, do you think we could potentially see like a two-year median duration of follow-up or?
or a year and a half in that kind of range.
you know, a year and a half, like, in that kind of range? Yes.
That's true. Okay. Excellent. All right. Thanks for taking my question. Thank you, Justin. Our next question comes from a line of Kelly Shih from Jefferies. Please proceed.
Hi, thank you for taking my question. This is Dave for Kelly Sheet. Actually, I have a question on GC 007 G in BALL in China. So you said data will be in 2023. Can you add some color on when the submission to an MPA is planned and maybe some color on market opportunity of GC 007?
We have observed very improved data in the phase one.
So we're going to share the data again later this year. We have more at on later.
I think that's about it. That's good.
Thanks everyone. Our next question comes from Emily Bodner from HC Wainwright. Please proceed.
Hi, thanks for taking the questions. I guess since you said you expect to finish the Phase 1B portion of the U.S. study in the first quarter of 2024, should we not expect any data updates from the Phase 1 this year? I guess kind of a follow-up on the durability questions.
maybe just tell us how you're thinking about what would be considered positive. I know previously you said 15.7 months was an estimate, but are you looking to see something around that range or could we potentially see something higher? And maybe now that you're advancing 12f into later stage studies, how are you kind of thinking about prioritizing?
Will we have any data released?
for Base 1B of 12F prior to first quarter of next year.
The second question is the
of the 29 patients IIT study.
What's the third part? Just prioritization of the rest of the pipeline for the year.
That's right. Wendy, do you want to take the first one, the 12F1B study?
Actually, I think you just mentioned about the completion will be the first phase 1B element will be 2024, first quarter. And then I think the data, we're just looking for that timeframe. So now it's early and the premature yet.
durability case we're going to explore the data I think we just mentioned about a couple people asking for in this year later on right either one the meeting or many scrapped way yeah
Yeah, we can provide more details about durability, but you can hear from us. We're very encouraged.
We can provide more details about durability, but you can hear from us. We're very encouraged.
I'm very confident. So let's look forward. Now the third part, which is prioritization. The 12F has been demonstrated such.
and safe, very outstanding safety profile, as well as the efficacy across about now total, what, 50 patients.
And across three indications, RMM, NDMM, URETA, NHL, we believe this dual targeting compound has very unique applicability in addition to hemoprological cancers.
there will be a possibility to cross the line to human knowledge indications because BCMA is CD19 or CD19 or end CD19. So we prioritize our resources and we like to focus on.
expansion of application of this product. Thank you very much.
You're welcome. And with that, our final question comes from the line of Lewis Chen from Cantor Fitzgerald. Please proceed.
Hi, this is Wayne for the we congrats on all the progress and thanks for squeezing. So, my first question is, do you think the face to portion of the US study for the GC 012. That could serve as a basis for accelerated approval. And then I also wanted to ask you have a lot of going on this year very very busy.
So what are your key most important readouts that you're looking forward to this year? Thank you. Yeah, two questions. Wendy, do you want me to take that one?
What are your key most important readouts that you're looking forward to this year? Thank you. It's two questions. Wendy, do you want me to take that one? Yes, go ahead. I'm going to try to leave the entrance and the entrance.
Okay. The phase two, after the phase two, 50 patients enrollment, are we looking at a breakthrough? It's very possible, of course.
But let's see from Phase 1b data, and we'll certainly look for that. I look forward to applying for that.
No, we.
We do have lots going on this year, particularly this year. Lots going on. R&D study in the U.S. and new programs entering clinical IT. And we are moving on bottling some of these new products.
R&D filing in the US as well as in China. But it's all being laid out nicely. They are stuck out with all the resources aligned. And of course the focus is continued to be to be able to do that without hesitation, pushing forward with the 12F.
on HANA-MM because that's going to demonstrate a lot of features of this product. And then additional application of this compound is sort of being laid out, newly diagnosed NHL and potentially immunology indication.
So these are sort of key focus, but then we're also very excited about a solid tumor program. With Claudia 18.2 is sort of proven target. Now our logic is very simple. If we add on my card.
device, would the efficacy be better, which is so much needed for Solitune. Now, for the true UCAR platform, we're continuing refinement of the UCAR-T technology as well as the product. And with the goal of.
extending the persistence, which is the key to off-the-shelf country products. And we do see very encouraging preclinical data in both.
solid tumor program as well as the UConn T program. And then we'll see now what's going to happen in preclinical model and we'd like to see in human model, in human studies. So it's a very exciting year and we're looking forward to see data coming out mid of the year and end of the year.
Got it. Thank you very much. Thank you. Thank you, Brad, again. You're welcome, Louis. I would now like to turn call back to Dr. William Chow.
Thank you again to everyone for joining us on the call. We are proud of the progress the GRACE-OUT team made over the past year. 2023 will be a critical year for us as we are on track to initiate our RRMM IND studies in the US and China.
We believe GrayCell is well positioned to deliver CAR T-cell therapy that can potentially transform the treatment landscape. We look forward to providing clinical data updates and sharing key pipeline and technology updates throughout the year.
Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.
I you.
At this time, all participants are in a listen-only mode.
After opening remarks, we will open the call for your questions.
Instructions for queuing up will be given at that time. I would now like to turn the call over to Dr. Kevin Chee, CFO . Please go ahead.
Good morning and welcome to Gray cell fourth quarter 2022 corporate update conference call on the webcast. Welcome to Gray cell fourth quarter 2022 corporate update conference call on the webcast call
With me today are Chris's founder and the chief executive officer, Dr. William Tao, our chief medical officer, Dr. Louis Dendy.
We're excited to discuss the progress of our differentiated clinical pipeline of CAR T therapies on today's call.
We also look forward to sharing with you our recent business developments and upcoming objectives as we head into 2023.
After our formal remarks, we will conduct a question and answer session.
This morning, Great Cell issued a press release announcing unaudited financial results for the quarter as the full year ended December 34, 2022. We encourage everyone to read this press release and we'd like to remind you that this call is being recorded for replay.
Please note that for certain information discussed on the call today, including financial data, clinical data, and future plans of our program, Research Management will be making forward-looking statements. Actual results could differ materially from those stated or implied by those forward-looking statements.
as a result of various important factors. And please refer to the Risk Factors section of our latest 20-hour filing with SEC for a full disclosure of these risks and the factors. This conference call contains time-sensitive information that's accurate.
only as of the date of this live forecast, March 13, 2023. retail undertakes no obligation to revise or update any forward-looking statement to reflect events or circumstances after the date of this conference call, except as may be required by acceptable securities laws.
I will now turn the call over to Grace of CEO , Dr. William Chow. William.
Thank you, Kevin. And again, welcome everyone to our fourth quarter 2022 corporate update conference call. It has been a very productive few months for us.
I will begin today's call with key pipeline updates. I will then turn the call over to our CMO, Dr. Wendy Lee, to provide insight into the two companies sponsored trials for GC012F in relapse refractory multiple myeloma that we plan to commence in 2023.
Thereafter, our CFO , Dr. Kevin Hsieh, will discuss our fourth quarter and a full year 2022 financial results. After our prepared remarks, we'll open the call to questions.
Let me start by emphasizing the high level of conviction that we have in the therapeutics and the commercial potential of our lead autologous CAR T candidate, DC012F, in hematology and potentially immunology indications.
Autologous CAR T therapy has now established itself as the most potent treatment for several hematologic malignancies. But significant unmet needs continue to exist for patients and physicians who are facing supply limits, long waste time, and high costs.
as well as calling for improved safety and durable efficacy.
These needs have been propelling the cartoon industry to move forward and innovate.
As Graycell would believe, 12F represents a next generation of autologous CACI therapy candidates.
and has the potential to push the boundary of Autologous Car-T on many fronts, such as manufacturing speed, safety, cost, and even durability of advocacy.
is comprised of younger, more fit T cells that are manufactured within 24 to 36 hours. Fast Cut not only helps to shorten patient wait time to weeks from months, but also provides key advantages.
in advanced cell quality and cost saving. Next, software features novel BCMA and CD19 dual targeting.
This is designed to enable the deepest response and durable efficacy based on the dual mechanism of action.
Our clinical data generated from 45 multiple myeloma patients has shown a consistent 100% MID negative rate in all patients treated with GC012F, which represents the deepest level of eliminating malignant cells in bone marrow.
And on the durability side, we plan to provide an important data update from our relapse to refractory multiple myeloma investigator initiated trial study around midyear.
And hopefully, that it will add to the expanding body of evidence supporting 12F's significant potential. I also hope to point it out that the dual targeting mechanism of action provides GC012F with wide applicability across diseases.
where either BCMA or and CD19 could be ending targets.
including multiple myeloma, NHL, and beyond, for example, in certain immunology indications.
Lastly, but very importantly, GC012F has demonstrated a highly differentiated safety profile in IIT studies. No neurotoxicity was observed in the 48 patients dosed in three studies under way in RMM.
newly diagnosed high-risk multiple myeloma, and in relapse, refractory non-Hodgkin informa. While the cytokine release syndrome, or CIS, observed in the studies has been mostly low-grade, it is also worthwhile highlighting that
The median onset of CIS is around six days across our MM studies. These safety features could potentially provide critical differentiation and benefits in earlier lines or outpatient settings.
Last month, we have announced that US FDA and China MMPA cleared our R&D applications.
which included our China IAT data. GrayCell has reached a very exciting juncture in its development life cycle as two company-sponsored studies evaluating 12-affeine RMM are on track to commence soon.
Advancing our lead FSCAR-T candidate towards a U.S. Phase 1B-2 clinical trial is a major milestone and we plan to initiate enrollment in the second quarter. The Phase 1-2 clinical trial in China is expected to commence in the third quarter of 2023. Our CMO, Dr. Lee, will provide additional details shortly.
In addition, we remain very excited about the data we have gathered so far in RIT studies. It is underway to evaluate GC0-12F in a newly diagnosed high-risk multiple myeloma patients. The first inpatient data from this trial was presented.
at an oral session of the ASH annual meeting in December 2022. We were overwhelmed by the very positive reception from the medical community on the data. SKOLs are optimistic about our candidates' potential in frontline settings. We continue to follow up this day.
and anticipate sharing additional data later this year. As a reminder, we also unveiled the first data from an ongoing IIT of GC012 for in-relapse refractory NHL at IHA in June 2022. We are continuing the enrollment and follow-up of these patients in ongoing study.
and plan to share the updated data at a medical meeting in 2023. Moving on to the off-the-shelf True UCAH platform, DC502 is our True UCAH-enabled CD19-CD7 dual-directed allogeneic CAR T therapy candidate being evaluated at the treatment site.
for RRBALL. At last year's EHOP, we presented updated IIT data, which shows three out of four treated patients achieved MID-negative CRI. This study is ongoing.
Next, moving on to our donor-derived CAR T. In October , we announced the dosing of the first patient in China registration of phase 2 trial evaluating GC-77G in an allogeneic CD19 targeted CAR T cell therapy. The dosing of the first patient in China registration of phase 2 trial evaluating GC-77G is derived
for the treatment of RRBALL patients who fail the transplant and may not be eligible for tautolase karti therapy.
We have observed highly encouraging safety and efficacy data in the Phase 1 portion, and we hope to share the data later 2023.
Lastly, SmartCART is our second generation technology for the treatment of solid tumors and utilizing a normal construct to take advantage of the suppressive tumor microenvironment and effectively combat solid tumors.
Preparations are underway for the IIT trial for the second SmartConT candidate. BC506 targeting quality 18.2 and enrollment is on track to commence in the coming months.
As we head into 2023, we are very optimistic about continued advancement of our highly differentiated CAR T platforms as we are on track to commence two company-sponsored trials, advance enrollment in ongoing studies, and push forward other initiatives.
We look forward to providing several clinical data updates at upcoming medical meetings throughout 2023. Now I will hand the call over to our CMO, Dr. Wendy Lee, to discuss our participation at ASH in December .
Wendy, please go ahead. Thank you, William. In the U.S., we plan to initiate a company-sponsored phase 1b and 2 clinical trial evaluating Gc012F for the treatment of relapsed and
and the Refractory Multiple Melanoma during the second quarter of 2023. We received clearance from the U.S. FDA for IND application in January 2023.
The phase 1b portion of the trial is designed to evaluate the safety and the tolerability of DC012F in two dose levels and to determine the recombinant phase 2 dose.
We plan to area approximately 12 patients who have received three or more prime lengths of therapy in the FIS1b portion at two dose levels. We plan to activate up to five to ten sites.
that are very experienced in conducting CAR T-12. We currently anticipate completing the phase one portion during the first quarter of 2024, and then holding an end of the phase one meeting with FDA shortly thereafter in 2024 to align on the next steps.
According to the company's sponsored trial in China, we plan to initiate elements in the FIF 1 and 2 trial evaluating GC 012F in RRMM during the third quarter of 2023.
The phase one portion of the trial is designed to evaluate the safety and tolerability of TC012F across two dose levels and to determine the RPTD. We plan to enroll approximately nine patients.
at one clinical site in China and anticipate completing elements in the phase 1 portion during the first half of 2024.
Last December , an oral presentation on the first clinical data from ongoing IIT evaluating GC012F in newly diagnosed multiple myeloma patients was conducted at the ARSH annual meeting.
The data demonstrated that GC012F achieved 100% overall response rate and 100% MRD activity in all 16 transplant eligible high-risk NDMM patients.
across all those levels. The safety profile was excellent as 75% of the treated patients did not experience any cytokine release syndrome. Also, no email effector cell associated.
neurotoxicity syndrome or other neurotoxicity of any grid have been observed.
We have received significant enthusiasm from the medical community since the ASH presentation.
As the data highlighted an impressive 100% ORR and 100% MRD negative in first-line patients that have multiple high-risk features and regardless of whether they have responded to the short induction therapy of two lungs.
of RVD before the infusion of GC012F. In contrast, the current standard of care for newly diagnosed multiple myeloma usually includes as many as four to eight rounds of induction therapy, which can be triplated such as.
RVD or quadruplets such as the direct TMMF plus RVD followed by autologous stem cell transplant and then a few years of maintenance therapy.
At the end of the transplant, SCR is typically 30% to 40%. An MRD negative rate could be between 20% to 50%. It's also worthwhile to mention that typically with the standard of care.
it can take a year or more between diagnosis and completing the transplant. While with CAR T, the median time from diagnosis to infusion of GC012F in the ongoing trial was less than five months.
So our data is among the first to demonstrate the material benefits CAR T can bring to the newly diagnosed multiple myeloma patients.
including shortening the diagnosis to treatment time, deepening the response, and maximizing the response rate.
All achieved with a good safety profile. We continue to follow the patients in our study to further evaluate the long-term benefits.
We are very encouraged by this initial data and currently evaluating the path forward for this indication.
I will now hand the call over to our Seattle, Dr. Kevin Hsieh. Kevin? Thank you, Wendy. Turning to our financials, I'd like to touch on a few financial trends.
As of December 31, 2022, the company had RMB 1,458.2 million for US dollar 211.4 million in cash and the cash equivalents and the short-term investments. We expect the cash yields for this year to be approximately 100 million USD.
2024. My loss attributable to ordinary shareholders for the three months ended December 31, 2022 with R&D $130.7 million, US dollar $18.9 million.
compared to RMB 128.6 million for the same period in 2021. My loss attributable to ordinary shareholders for the full year ended December 31, 2022.
with RMB 607.5 million or US dollar 88.1 million.
compared to RMB 453.7 for the same period in 2021.
Research and development expenses for the three months ended December 31, 2022, with RMB $113.1 million, with U.S. dollar $16.4 million, as compared to RMB $107.6 million, for the same period in 2021. The full year ended December 31, 2022. Research and development expenses for the three months ended December 31, 2022.
development and the clinical trial, as well as higher pay-all and the personnel expenses attributable to increased headcount and the higher facility related costs in support of continued expansion of research and development activities.
With that, I'd like to turn it back to the operator to open the session for your questions. Operator? The floor is now open for your questions. To ask a question at this time, please press star 1 on your telephone keypad. If at any point you'd like to withdraw from the queue, please press star 1 again.
You will be provided the opportunity to ask one question and one further follow-up question. We'll now take a moment to render our roster. Our first question comes from the line of Yigal Neshabat from Citi. Please proceed.
Hi, team. This is Carly. Thanks so much for taking our questions. First, can you comment on the vein to vein time you are anticipating for GC012F in the U.S. Phase 1 with the current process and quality control procedures that you have in place? And then I guess how much further do you believe that can be optimized as you move into the next phase?
later stage development and eventually the commercial setting. Hi, Carly. Very good question. The first part is very good. The second part is better. And let me sort of put together pieces so that you understand, you know, because each other we're probably using different definitions.
Let's say delivery time, meaning we receive the sample and return the cells to the hospital. That's supposed to be seven days. However, you add on logistics and then QC everything. We have 12 days now.
Before I get to link for depletion, okay. The releasing test in our hand is five days, seven days.
However, in the US, the test is being done by third-party laboratory. So that will add on a few more days.
So it's not going to be seven days of the EHCU test. It's been probably nine days, 10 days, and perhaps even longer. So that part I can't give you a definitive answer yet.
So basically it's three days manufacture from receiving and by having the belt ready plus
a week to seven or some days to ten days of testing days. Now, vein to vein time.
including lymphoid depletion. So that will add on three days plus. So total together I would say about probably up to three weeks.
The second part of the question is, is there any possibility to optimize? Yes, of course. Moving forward, we will establish in-house quote-unquote, the tests can be done within CDMO.
then it will shorten the time of logistics shipping in and out. Okay, great. That's super helpful. And then we just had one follow-up. I guess we've heard from some companies that... No, sorry. Oh, yeah. Sorry, there is one more, one minor point I would like to add on here. Oh, sure. If we could further optimize...
the releasing test, let's say shortened from seven days to five days, for example, then here is some area we can optimize as well. Okay, perfect. And then our follow-up was just on enrollment. I guess we've heard from some companies that enrolling late-line myeloma patients in the US is becoming increasingly difficult given the availability of the BCMA by specifics. So just curious any feedback you're hearing from K-Wells around this and...
what steps you can take to facilitate enrollment in the Phase I-II. Thank you so much. Sure. Wendy, do you want me to try first, and then you can... Yeah, go ahead. Okay. Yeah, go ahead. My signal is not very good. It's just, yeah, please back to you. That's why we, what we hear is...
slightly different. Perhaps the PIs, the carers we have been working with are very enthusiastic and seems to us that phase 1B, 12 patients enrollment, is not going to be an issue. No.
Hopefully, our sites we select are very experienced, that we know. Hopefully, the patients that enroll in that site are also looking for fast delivery products like GC0-12F.
But anyhow, so far, we don't have any special concern about the speed of enrollment. Does that answer your question? Wendy, do you have anything to add on?
And also perfect.
Thanks, Cardi. Did we answer your question? No.
Our next question comes from the line of James Shin from Wells Fargo. Please proceed. Please proceed.
Good morning, guys. Thanks for taking my question. Just wanted to touch base on comments regarding a partnership and it didn't seem quite, it didn't seem mentioned in the press release and then I have a follow up. Yeah, you haven't seen the press release. You're right. I would wish, you know, it comes with the material.
Since our ASH presentation of newly diagnosed multiple myeloma studies and the immediate news about IND filing, we do receive positive response and interest.
but I can review more details in that direction. But please be ensured that on top of our.
help our priority. This is the right way to go. So we'll continue to pursue that.
Got it. And then for the Quadrant program, what sort of...
Would you expect to see responses this earlier? Is this sort of like a proof of concept? Can you say anything on your expectations for solid tumors for cell therapy?
You mean administration of healing
You mean maca or solid tumor? Yes, GC506. Okay.
Yeah, the target is claudia 18.2. We will initiate clinical IIT first, which will commence very soon, I believe.
The target is claudia 18.2. We will initiate clinical IIT first, which will commence very soon.
So we'll have reasonable time to assess solid tumor response. But this will take, I don't know, six months to validate.
with the new product. Okay, all right, thank you. Yeah, great. We haven't published any data including clinical.
clinical data mechanism studies so I can't really comment on details but the purpose of this whole program or the objective of the new design on Claudia 18.2 plus the smart device is to enhance the efficacy and we believe for phytoma you do need
a strong push of the CAR T cell into tumor tissue to combat the suppressive environment. So hopefully with the additional smart design plus this widely recognized target 18.2, we're going to see some signals.
of the CAR T cell into tumor tissue to combat the suppressive environment. So hopefully with the additional smart design, plus this widely recognized target 18.2, we're gonna see some signal. But we didn't have to wait.
Thank you for that. Our next question comes from the line of Justin Zellin from BTIG. Please proceed. The last question has come in
Hi, good morning guys. Thanks for taking the question and congrats on the progress here. I had a question just on the IIT durability data that we're expecting later this year. Are you targeting a medical meeting for disclosure of that data?
or could that come as kind of a company event here? And I have a follow up. Yeah, Wendy, I think that's for you. Yeah, that's right. Yeah, we're going to have, yeah, explore the data later this year for the meeting or the managed craft. So yeah, we're
We're looking forward to popping those information later, but within this year. May I add on? You hear from Dr. Lee that both papers...
and presentation conference plans. So whichever come out first. Now it's possible that the year if.
you know, ASCO and EHI, if these, we can get in on time, and if the paper published earlier than that. So it's all ballpark, it's in ballpark within this year.
Got it. Okay, that makes sense to me. And then for the 29 patients, I think the last update we got last year, the median duration of follow-up was approaching a year. For this next update, do you think we could potentially see a two-year median duration of follow-up or a year and a half in that kind of range?
Yes. That's true. Okay. Okay. Excellent. All right. Thanks for taking my question. Thank you, Justin. Our next question comes from the line of Kelly Hsieh from Jefferies. Please proceed. We'll take you from our Laura
Hi, thank you for taking my question. This is Dave for Kelly Sheet. Actually, I have a question on GC007G in BALL in China. So you said data will be in 2023. Can you add some color on when the submission to an MPA is planned and maybe some color on market opportunity of GC007G?
to encourage data in the phase one. So we're going to share the data again later this year.
Thank you.
We have more at on later.
I think that's about it. That's good. Thanks everyone. Our next question comes from Emily Bodner from HC Wainwright. Please proceed. Hi, thanks for taking the questions. I guess since you said you expect to finish the Phase 1B portion of the U.S. study in the first quarter of 2024, Is there any new highlights from this process about U.S.llo freshman Mark
Should we not expect any data updates from the Phase 1 this year? I guess kind of a follow-up on the durability questions. Maybe just tell us how you're thinking about what would be considered positive. I know previously you said 15.7 months was an estimate, but are you looking to see something around that range or could we potentially see something higher?
And maybe now that you're advancing 12F into later-stage studies, how are you kind of thinking about prioritizing the rest of your pipeline for development? And is there any other indications besides ALL that we could see data this year? Thanks. There are about three questions. First one, will we have any data released?
for Base 1B of 12F prior to first quarter of next year. The second question is the
12f prior to first quarter of next year. The second question is the
of the 29 patients, IT study. What's the third part? Just prioritization of the rest of the pipeline for this year. All right.
That's right. Wendy, do you want to take the first one, the 12F1B study?
Actually, I think you just mentioned about the completion will be the first phase 1B element will be 2024, first quarter. And then I think the data, we're just looking for that time frame. So now it's early and the premature yet.
So, the second question. The 12F durability. The durability actually we're very confident from our 29 you know our patients from the IT already. We got a very good, you know, data right and also durability so we're going to explore the data. I think we just mentioned about a couple people asking for in this year later on. Right. Either one of them meeting or many many scrapped. Right. Yeah.
Yeah, we can provide more details about durability, but you can hear from us. We're very encouraged, very confident. So let's look forward. Now the third part, which is prioritization, the 12F has been demonstrated such.
and safe, very outstanding safety profile, as well as the efficacy across about now total, what, 50 patients? And across three indications, RMM, NDMM, URETA, NHL, we believe this dual targeting compound has very unique.
applicability. In addition to hematological cancers, there will be a possibility to cross the line to immunology indications.
because BCMA is CD19 or CD19 or and CD19. So we prioritize our resources and we like to focus on the extension of application of this product.
Congrats on all the progress and thanks for squeezing. So my first question is, do you think the phase two portion of the US study for the GC012, that could serve as a basis for accelerated approval? And then I also wanted to ask, you have a lot going on this year, very, very busy.
So what are your key most important readouts that you're looking forward to this year? Thank you. Yeah, two questions. Wendy, do you want me to take that one? Yeah, go ahead. Okay.
The phase two, after the phase two, 50 patients enrollment, are we looking at a breakthrough? It's very possible, of course. But let's see from phase 1B data and we'll certainly look for that.
I look forward to apply for that. Now, we do have lots going on this year, particularly this year, lots going on. R&D study in the US and new programs entering clinical IT, and we are moving on bottling some of these new products.
R&D filing in the US as well as in China. But it's all being laid out nicely. They are stuck out with all the resources aligned. And of course the focus is continuing to be without hesitation, pushing forward with the 12F, on high MM, because that's going to demonstrate a lot of features of this product.
And then additional application of this compound is sort of being laid out, newly diagnosed, NHL, and potentially immunology indication. So these are sort of key focus. But then we're also very excited about a solid tumor program. The coordinating point two is sort of proven target.
Now, our logic is very simple. If we add on smart car device, would the efficacy be better? Which is so much needed for Solitune, right? Now, for the true UCAR platform, we're continuing refinement of the UCAR-T product technology as well as to the product.
and with the goal of extending the persistence, which is the key to off the shelf country product. And we do see very encouraging preclinical data in both.
solid tumor program as well as the UConn T program. And then we'll see now what's going to happen in preclinical model and we'd like to see in human model, in human studies. So it's a very exciting year and we're looking forward to see.
data coming out mid of the year and end of the year. Got it. Thank you very much.
middle of the year and end of the year. Thank you very much.
end of the year. Thank you very much. Thank you.
I would now like to turn the call back to Dr. William Chow. Thank you again to everyone for joining us on the call. We are proud of the progress the Gracer team made over the past year.
2023 will be a critical year for us as we are on track to initiate our RMM IND studies in the US and China. We believe GrayCell is well positioned to deliver CAR T-cell therapy that can potentially transform the treatment landscape. We look forward to providing clinical data updates.
and sharing key pipeline and technology updates throughout the year. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.