Q4 2021 Gracell Biotechnologies Inc Earnings Call
Operator: Ladies and gentlemen, thank you for standing by. Welcome to the Gracell Biotechnologies fourth quarter and full year 2021 conference call. At this time, all participants are in a listen-only mode.
Ladies and gentlemen, thank you for spending by welcome to the Grenfell Biotechnologies fourth quarter and full year 2021 conference call. At this time all participants are in a listen only mode.
Operator: After the opening remarks, we will open the call for your questions. Instructions for queuing up for questions will be given at that time. I'll now turn the conference call over to Dr. Kevin Xie, CFO. Please go ahead. Good morning, and welcome to Gracell's fourth quarter and the full year 2021 earnings conference call and webcast. With me today are Gracell's founder and chief executive officer, Dr. William Tsao, and our chief medical officer, Dr. Martina Surge.
After opening remarks, well open the call for your questions instructions for queuing up for questions will be given at that time.
Now I'll turn the conference call over to Dr. Kevin Shea CFO . Please go ahead.
Good morning, and welcome to <unk> quarter, and full year 2021 earnings conference call and webcast.
With me today, <unk>, founder and Chief Executive Officer, Tom Williams.
And our Chief Medical Officer Welcome Martinez.
Operator: We're excited to discuss our innovative technologies and the breakthrough clinical pipeline of CARPY therapies on today's call. We also look forward to sharing with you our recent business developments and upcoming targets for 2022. After our formal remarks, we'll conduct a question and answer session. This morning, Retail issued a press release announcing unaudited financial results for the quarter ended December 31, 2021.
We're excited to discuss our innovative technology and breakthrough clinical pipeline of car T therapies on today's call.
We also look forward to share with you our recent business developments and upcoming targets for 2022.
After our formal remarks, we will conduct a question and answer session.
This morning, <unk> issued a press release announcing unaudited financial results for the quarter ended December 31 2021.
Operator: We encourage everyone to read this press release. And we'd like to remind you that this call is being recorded for. Please note that for certain information discussed on the call today, including financial data, clinical data, future plans of our programs, Results Management will be making forward-looking steps. However, actual results could differ materially from those stated or implied by this forward-looking statement as a result of various important factors. And please refer to the risk factor section of our latest 20th volume, Risk SEC, for full disclosure of this risk and factor.
We encourage everyone to read the press release and will last will remind you that this call is being recorded for replay.
Please note that certain information discussed on the call today.
Financial data clinical data future plans of our program.
Just imagine that we'll be making forward looking statements actual results could differ materially from those stated or implied by these forward looking statements as a result of various important factors.
And please refer to <unk>.
Risk factors section of our latest 20-F filings with SEC for a full disclosure of the risks and factors.
Operator: The conference call contains time-sensitive information that's accurate only as of the date of this live forecast, March 14, 2022. Gracell undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except, as may be required by security, I will now turn the call over to Bristol CEO, Dr. William Tsao. William?
The conference call contain time sensitive information that is accurate only as of date of this my forecast March 14 2022.
Lisa undertakes no obligation to revise.
Any forward looking statements to reflect events or circumstances. After the date of this conference call, except as may be required by Securities law.
I will now turn the call were reached our CEO Dr. William William.
William.
Thank you Kevin.
Dr. William Tsao: Thank you, Kevin. And again, welcome everyone to our fourth quarter and full year 2021 earnings conference call. Gracell has made substantial progress over the last year and continues to deliver across corporate, clinical, and operational initiatives. I will elaborate on some of the key achievements and updates.
And again welcome everyone to our fourth quarter and full year 2021 earnings conference call.
Great. So have made substantial progress over the last year and it continues to deliver across corporate clinical and operational initiatives.
I won't elaborate on some of the key achievements and updates.
Dr. William Tsao: Following this, I will turn the call over to our Chief Medical Officer, Dr. Martina Search, to discuss our pipeline developments and regulatory advancements in the U.S., and then to our Chief Financial Officer, Dr. Kevin Xie, to discuss financial results. And at the end, I will share our anticipated milestones for the year to come. Since our last corporate update call on August 27, 2021, And we have continued to make progress across our innovative portfolio of autologous and allogeneic CAR T cell therapy, built upon our rich cell therapy and gene editing expertise and proprietary fast car, true car, and smart car technology platforms across multiple difficult-to-treat hematological malignancies and solid tumors.
Following this I will turn the call over to our Chief Medical Officer, Dr. Mattina search to discuss our pipeline developments.
Regulatory advancements in the U S and then to our Chief Financial Officer, Dr. Kevin Shea to discuss financial results.
And.
I wish it our anticipated milestones for the year to come.
Since our last corporate update call on August 27, 2021.
And we have continued to make progress across our innovative portfolio and.
Allogeneic car T cell therapies buildup.
Built upon our rich cell therapy, and gene editing expertise and proprietary first call to call and smart car T technology platforms across multiple difficult to treat hematological malignancies and solid tumors.
Dr. William Tsao: We are continuing to advance our fast autologous CAR T platform, which is designed to overcome challenges of conventional CAR T therapies by significantly shortening cell manufacture time from weeks down to next day. Importantly, this also contributes to enhanced T-cell fitness, as this is supported by the vast data from our preclinical studies. Because our process manages to preserve T cell fitness.
We are continuing to advance our ophthalmic.
<unk> coffee platform, which is designed to overcome challenges of conventional car T therapies by significantly shortening cell manufacture time from weeks down to next day.
Fortunately this also contributes to enhance T cell fitness. This is supported by the vast data from our preclinical studies.
Our process managed to preserve T cell fitness.
Dr. William Tsao: Our cells are very potent, and a therapy only needs a small number of cells in comparison to others, eliminating the need for ex vivo expansion, which could result in cell exhaustion. If you compare our dose to other CAR T therapies, our dose ranges from one-third to one-hundredth of other doses. And because our cells are more potent, and expansion happens in vivo, the optimal environment for T cell proliferation, the peak of expansion of our CAR T cells reaches three times that of certain marketed CAR T cell products. And our AUC Area Under Curve is about 2.5 tons of it.
So a very potent and a therapy only needs a small number of cells in comparison to others, eliminating the need of ex vivo expansion, which could result in some exhaustion.
If you.
Those two other car T therapies, our dose ranges from one third to 102 other dose.
And because ourselves a more potent and expansion happens in vivo the optimal environment for T cell proliferation.
Peak of expansion of our car T cells reaches three times that number.
Certain market is kind of a T cell product.
And our AUC area and kind of is about two five times.
Dr. William Tsao: In November of 2021, our lead FASCAR-T candidate, GC012F, was granted orphan drug designation by the US FDA for the treatment of multiple myeloma. TopF is a novel, dual-targeting product candidate, specific for two different antigens, DCMA and CD19, which we believe has the potential to be highly efficacious. COFFS has demonstrated fast, deep, and durable responses in patients with relapsed refractory multiple myeloma in an ongoing IIT study in China, with most patients on the study being high risk, according to MSMAS 3.0 criteria, are difficult to treat in patient populations.
In November of 2021, our lead car T.
Candidate <unk> zero 12 months.
Was granted orphan drug designation by the U S FDA for the treatment of multiple myeloma.
<unk> is a novel dual targeting product candidates.
Pacific for two different antigens.
And the CV 19.
Which we believe has the potential to be highly efficacious.
<unk> has demonstrated fast deep and durable responses in patients with relapsed refractory multiple myeloma and an ongoing study in China with most patients on study being high risk According to <unk> criteria.
<unk> to treat patient population, we're very excited about it being granted orphan drug designation for the treatment of multiple myeloma on a U S. FDA.
Dr. William Tsao: We're very excited about it being granted often drug definition for the treatment of multiple myeloma by the US FDA, as it qualifies Gracell as the sponsor of the therapy for certain development incentives. Dr. Search will share more about 12F and expand on its progress shortly.
Ask me to quantify great Joe as the sponsor of this therapy for certain development incentives.
Doctor search well share more about 12 go ahead and expand its progress shortly.
Dr. William Tsao: We have extended our timeline for R&D submission in the U.S. for TC012F for RRMM to the second half of 2022. While we have made significant progress with our tech transfer from our Suzhou GMP manufacturing facility to the U.S. CDMO, this revised timeline reflects the impact of the industry-wide high demand for cell therapy manufacturing capacity. The verification runs are producing quality cells, and we continue to work closely with our CMO to move forward. For the R&D file in the US, we are on track to submit it by the end of the year.
We have extended our timeline.
Some Michigan and the U S G.
<unk> zero 12 four.
Then to the second half 2022.
While we have made significant progress with our tech transfer from our shoe towards GMP manufacturing facility to the U S. CMO. This revised timeline reflects the impact to the industry wide high demand since therapy manufacturing capacity.
The verification runs producing quality sales and we continue to work closely with our CMO to move forward.
For the <unk> in the U S. We are on track to submit.
End of the year 90, following and a further clinical development of <unk>.
Dr. William Tsao: The R&D filings and further clinical developments of 12F are a priority of Gracell. Our exciting advancement with 12F candidates is that we have dosed multiple patients in China in a phase one IIT study evaluating 12F in a new indication, relapsed endopractic B-cell non-Hodgkin's lymphoma, NHL. 12F is the first BCMA CD19 dual targeting CAR-T in human trials for BNHL. We have a strong rationale and preclinical data to support this novel design. This is consistent with Gracell's goal of innovation and a focus on pioneering best-in-class candidates.
A priority of greystone.
Our exciting advancement of 12 five candidates is that we have dosed.
Our people patients in China Phase <unk> study evaluating <unk> in a new indication.
And the refractory b cell non Hodgkin lymphoma NHL.
<unk> is the first <unk> CD 19 dual targeting car T in human trials will be NHL.
We have a strong rationale and preclinical data to support this design.
This is consistent with great sales goal of innovation and a focus on pioneering best in class candidates.
Dr. William Tsao: Turning to our allogenetic 2U CAR platform, we have an IAT study underway for CD19-CD7 dual-directed CC502 in adult patients with B-cell malignancies, including BALL, and a plan to present early first-in-human data from this study at AACR in April. We're very excited about this new candidate, as it is the first of its kind as of the CD19-CD7 dual car allogeneic CAR-T and exemplifies the TrueU CAR platform's broad applicability enabled by the novel dual direct-to-the-CAR design.
Turning to our allogeneic <unk> car platform, we have an NIH study underway or CD 19, <unk> dual directed GC firewall tune in adult patients with B cell malignancies, including AML and plan to present early first in human data.
From this study at ACR in April .
We're very excited about this new candidates.
It is the first of its kind as a CD 19, <unk> seven dual call allogeneic car T and exemplify the true Ya com platforms broad applicability enabled by the novel due directly to the car design.
Dr. William Tsao: As a reminder, we shared data from the preclinical studies of GC502 last year at ASH. DC502 displayed strong anti-tumor potency and suppression of host versus graft response. For example, GC-502 showed superior CAR T-cell expansion and also cytotoxicity, including in a very demanding tumor re-challenge model. Additionally, it demonstrated robust activity in killing allogenetic T and NK cells to help suppress host versus one-after rejection. We also compared it with CD19 CAR-T control, and the results showed very strong potency in animal models.
As a reminder, we shared data from the preclinical studies of <unk> pharma to last year at Ash.
<unk> displayed strong antitumor potency and suppression.
Versus the graph the response.
For example, <unk> power <unk> showed superior comp system expansion and also cytotoxicity.
Including a very demanding tumor re challenge model.
Also demonstrated robust activity in killing Endogenetic T and NK cells to help suppress host versus graft rejection.
We're also compounded with CD 19 car T control.
Dr. Martina Search: We look forward to sharing the exciting early, first in human data next month. As 2022 unfolds, we will continue to build on our solid progress achieved so far. Toward the end of the prepared remarks, I will share our anticipated milestones for this year. Now, I will hand over the call to our Chief Medical Officer, Dr. Matina Search, to discuss the pipeline in our clinical program. Matina, please.
The results showed very strong potency in animal models, we look forward to sharing the exciting early first in human data next month.
Yes, 2022 outflows, we will continue to build on our solid progress achieved so far.
Towards the end of the prepared remarks, I will share our anticipated milestones for this year.
Now I will hand over the call to our Chief Medical Officer, Dr. Martina search to discuss the pipeline and our clinical programs.
Martina please.
Thank you William.
Dr. Martina Search: Thank you, William. Gracell is currently developing a rich pipeline of multiple autologous and allogeneic product candidates for the treatment of different types of cancer. Our lead program is GC012F. In 2021, we applied for and were granted orphan drug designation for GC012F by the US FDA for the treatment of multiple myeloma. We continue advancing our lead candidate, GC012F, in relapsed and or refractory mild myeloma, as well as into earlier lines of therapy. We have previously reported preliminary clinical data at ESCO 2020, ESCO 2021, and EHA in 2021 in 19 patients, demonstrating fast, deep, and durable responses at all dose levels in a very difficult-to-treat patient population.
<unk> is currently developing a rich pipeline of multiple autologous and allogeneic product candidates for the treatment of different types of cancer.
Our lead program is <unk>.
In 2021 be applied and were granted orphan drug designation for <unk> by the U S. FDA for the treatment of multiple myeloma.
We continue advancing our lead Ken is that key season, you had 12 best in relapsed and refractory multiple myeloma as well as into earlier lines of therapy.
We have previously reported preliminary clinical data at <unk> 2020, ESCO 2021 and 2021.
19 patients demonstrating.
Deep and durable responses in all dose levels and are very difficult to treat patient population.
Dr. Martina Search: 95% being high-risk patients based on MSMART3 criteria. A data cutoff, January 12, 2021. Overall response rate among these 19 patients was 94.7%, with all responses being VGPR or better. Additionally, 84.2% out of the total of 19 treated patients achieved stringent complete response, SCR, the deepest response possible. 100% of MRD-accessible patients achieved MRD-negative. The Safety Profile of the Zero Club F was consistent with previous findings and mostly lower grade cytokine release syndrome, mostly low grade 1 or 2, with a medium time to onset of six days ranging from 2 to 10 days. No grade 4 or grade 5 CRS was observed.
95% in high risk patients based on <unk> III criteria.
At data cutoff generated 12, 2021 overall response rate. Among these 19 patients plus 94, 7% with all responses being <unk> or better.
84, 2% out of the total of 19 treated patients achieved stringent complete response SCR the deepest respond as possible.
100% of MRV assessable patients achieved <unk> negativity.
The thank you profile.
And your 12 Beth.
Consistent with previous findings and predominantly lower grade cytokine release syndrome, mostly low grade one not sure what the median time to onset of six days ranging from two to 10 days.
No grade four Crs.
Prs <unk>.
Dr. Martina Search: And also, importantly, we did not observe any icons of any grade. Today, we believe this data is very promising and highly competitive, both for efficacy and safety. In addition to the excellent preliminary outcome, there are several key differentiators that highly distinguish GC012F from the current landscape, the first one being BCMA's CD19 dual-target. The second very important part is the much-shortened manufacturing time.
And also importantly, we did not observe any icons of Ami.
<unk>.
To date, we believe this data is very promising and highly competitive both for efficacy and safety.
In addition to the excellent preliminary outcome. There are several key differentiator that's highly distinguished Gcs fall back from the current landscape.
The first one being the CMA CD 19 dual targeting.
Second very important part it's a much shortened manufacturing time.
Dr. Martina Search: 22 to 36 hours, which may lead to a much faster treatment of patients without the need for bridging therapy and ultimately may lead to reduced health care. In addition, we have extended the indication for GC012F to BNHL and are currently enrolling patients into an IIT study in China. G.C. Zero Troll Pass is the first PCMA CD-19 Dual Targeting Cartier in Human Trails for the NHL. Most BNHL cells express VD19, and data also suggest that 39% to 97% of clinical NHL cell samples also express DCMA.
<unk> to 36 hours, which may lead to a much faster treatment of patients without the need of switching therapy, and ultimately may lead to reduce health care costs.
In addition, we have extended the indication for <unk> to be NHL and are currently enrolling patients into an Iot study in China.
She says you are talk F is the first <unk> CD 19 dual targeting car T in human trials for BNS shelf.
Most DNN shelf belt Express CD 19, and data also suggests that 39% to 97% of clinical NHL cell samples also express <unk>.
Dr. Martina Search: By simultaneously targeting DCMA and CD19, GC12S is designed to improve efficacy outcomes in relapsed refractory BNHL patients. In preclinical studies, GC012F has demonstrated very encouraging capabilities, including specific and dose-dependent killing of CD19 and or BCMA-positive tumor cell life. Moving on to the TrueUka platform, our allogeneic uka tea derived from tea cells from healthy donors as an off-the-shelf ka tea therapy.
By simultaneously targeting.
CD 19, <unk> 12.
<unk> is designed to improve efficacy outcome in relapsed refractory NHL patients.
And the preclinical studies <unk> demonstrated very encouraging capabilities, including specific and dose dependent killing of CD 19, and RBC handmade positive tumor cell lines.
Moving on to the true you complex form our allogeneic <unk> car T derived from T cells from healthy donors estimate off the shelf catchy therapy.
Dr. Martina Search: This novel design of a dual-directed car utilizes one car to be a CD7 car intended to suppress host versus graft. This car has been optimized for induction of appropriate immunosuppression. With this construct, TRU-UCA is designed to be administered without the need for additional immunosuppressive therapies after standard lymphodepletion and offers further benefits and cost savings, potentially, and potentially safety. The second car is intended to target Kempf herself. The second car is intended to target Kempf herself.
Its novel design of a <unk> directed car utilizes one call to be a CD seven car intended to suppress host versus graft.
This call has been optimized transaction of appropriate immuno suppression.
With this construct true you cut is designed to be administered without the need of additional immunosuppressive therapies.
After stand that depletion and offers further benefits and cost savings potentially and potentially safety.
The second call is intended to target cancer cells.
Dr. Martina Search: The second car can be switched to target different cancer antigens, and this potentially gives the true U-car platform a broader applicability. The second car can be switched to target different cancer antigens, and this potentially gives the true U-car, DC-027 is our true Yuka enables CD-7 targeted Carti Cell therapy for the treatment of teaser acute lymphoblastic leukemia, KALL. We have previously reported promising efficacy and safety data at AACR 2021 and have since added many more patients to the study. Currently, we are targeting regulatory interactions globally and in China over the next 12 months.
The second car can be switched to target different cancer antigens and this potentially gets the true you car platform a broader applicability.
D C zero 2007.
Im sure you caught enabled <unk> targeted car T cell therapy for the treatment of T cell acute lymphoblastic leukemia.
A L L.
We have previously reported promising efficacy and safety data at ACR 2021, and Epson added many more patients to this study.
Currently we are targeting regulatory interactions globally and in China. During the next 12 months.
Dr. Martina Search: As William mentioned, we are very excited about the new and second candidate on the Pre-U Cup platform, GC502, which is the CD19, CD7 dual-directed Elegenate, Carti Therapy for B-Celner-Lignan. While we have been very encouraged by the profile of GC027, GC502 is our first product candidate to truly demonstrate the potential and wide applicability of a true UCAR platform to different We believe 502 is a promising off-the-shelf product platform, enabling the CD7 car to suppress host versus graft rejection response, while we added the second car, a CD19 car, to target cancer cells.
As William mentioned, we are very excited about the new and second candidate on the Truecar platform GC 502, which is the CD 19, CD seven directed allogeneic car T therapy for B cell malignancies.
While we have been very encouraged by the profile of cheeses newer 27 GC. Five also is our first product candidates to truly demonstrate the potential and wide applicability of virtual you cut platform two different types of cancer.
We believe five O two as the promising off the shelf product platform, enabling the C. DS seven comp to suppress host versus graft rejection response, while we added the second call of CD 19 car to target cancer cells.
Dr. Martina Search: CD7 car will help create the environment for the car T-cells to extend without additional immunosuppressive agents. We shared pre-clinical data of 502 at Ash 2021, which showed robust expansion and efficacy in patients. We will be presenting the first human clinical data at AACR in April. Our most advanced program is GC007G. Currently, a registrational phase 1, 2 clinical trial under a Chinese IND is ongoing for the treatment of relapsed refractory BLL patients.
<unk> seven <unk> will help create the environment for the car T cells to expand without additional immunosuppressive drugs.
We shot preclinical data of 502 at Ash, 2021, which showed robust expansion and efficacy in patients.
We will be presenting the first in human clinical data at ACR in April .
Our most advanced program is <unk> <unk>.
Currently our Registrational phase one two clinical trial and that China IMD is ongoing for the treatment of relapsed refractory B L. L patients.
Dr. Martina Search: We anticipate to soon be commencing the phase 2 part of the study. TC007G is a novel treatment option for patients that have relapsed after transplant and may not be eligible for autologous CAR T therapy. GC007G represents a new approach and is manufactured using healthy donor-derived HLM-matched T-cells. Offering an advantage over a patient's own T-cell, Beyond the programs discussed today, we have a rich, exciting, early-stage pipeline of product candidates based on our FastCar, TrueUCar, and SmartCar technology platforms for several indications, including solid tumors and hematological malignancies that we continue to evaluate We are on track to commence and rolling out a China IIT study for GC503 and nasal cells in positive solid tumors, including ovarian cancer, in 2022.
We anticipate to soon be commencing the phase II part of the study.
<unk> is a novel treatment option for patients that have relapsed after transplant and may not be eligible for autologous car T therapy.
<unk> represents a new approach and is manufactured using healthy donor derived HLA matched T cells.
During an advantage of a patients own T cells.
Beyond the programs discussed today, we have a rich exciting early stage pipeline of product candidates based on our Pascal <unk> and smart car technology platforms for several indications, including solid tumor and metallurgical malignancies that we can.
To evaluate move forward into the clinic.
We are on track to commence enrolling in a China IHS study for GBP, five or three and measle selling positive solid tumors, including ovarian cancer in 2022.
Dr. Kevin Xie: With these additional indications, we are striving to complete our platform to include not only hematological malignancies but also solid tumors, a hard-to-achieve goal for the industry today. In addition, we are expanding our teams, including regulatory and clinical operations in the United States to meet our demand. I will now pass it over to Kevin to discuss our R&D and manufacturing facilities and financial results.
With these additional indications we are striving to complete our platform to include not only how much illogical malignancies, but also solid tumors are hard to achieve for the industry today.
In addition, we are expanding our teams, including regulatory and clinical operations in the United States to meet our demand.
I will now pass it over to Kevin to discuss our R&D and manufacturing facilities and our financial results Kevin.
Thank you Martina.
Dr. Kevin Xie: Thank you, Martina. Our U.S. expansion is currently underway, with ongoing hiring being made to grow our research clinical operations, regulatory, and operations team. In China, we're expanding our manufacturing capability by building a new facility in Suzhou, in addition to our state-of-the-art 66,000 square feet GMP manufacturing facility designed for fully-closed production capabilities to reduce contamination risk and optimize production. Our manufacturing and operational capabilities are designed to improve both the speed and availability of our cell therapies so that our treatment can be available widely and rapidly to the cancer patients who need it.
Our U S expansion is currently underway.
Ongoing employment is being made to grow our research clinical operations regulatory and operations teams.
China, we're expanding our manufacturing capability building.
We are building a new facility in Suzhou in addition to our state of art.
6000 square feet GMP manufacturing facility.
Designed for 40 closed production capabilities to reduce contamination risk and optimize cost and efficiency.
Our manufacturing and operational capabilities are designed to improve both the speed and availability of our cell therapies. So that our treatment can be available widely and rapidly.
Cancer patients who need them.
Dr. Kevin Xie: Turning to our finish [inaudible] I'd like to touch on a few financial trends, as of December 34, 2021, we had RMB 1 billion and 829 million, for US dollar 287 million in cash, and the cash equivalent and short-term investment were very well funded with Cash Runway into 2024. We expect the cash use for this year to be approximately U.S. dollars 100 million to 120. Primarily to fund our R&B and clinical programs in the U.S. and China, to support our IMD filings, and to support expansion of our GMP manufacturing facilities in Suzhou, that loss attributable to ordinary shareholders for the three months ended December 31st, 2021 was RMB 128.6 million, for a U.S. dollar 20.2 minutes, compared to R&D 99.9 million for the same period in 2020 That loss attributable to ordinary shareholders in the full year 2021 was RMB453.7 million, or US dollar 71.2 million, compared to RMB 274.6 million for the same period in 2020.
Turning to our financials.
I'd like to touch on a few financial trends.
As of December 31, 21.
We had RMB 1 billion an eight.
801 9 million.
For our U S dollar 287.
Cash and cash equivalents and short term investments.
Well, we're well funded with cash runway into 2024.
We expect the cash use for this year to be approximately U.
U S dollar of 100 million to a 100 point here.
Primarily to fund, our R&D and clinical programs in the U S and China.
To support our R&D filings and to support expansion of our GMP manufacturing facility in Suzhou.
Net loss attributable to ordinary shareholders for the three months ended December 31, 2021 was RMB $128 6 million.
U S dollar 22 minutes.
Compared to RMB $99 9 million for the same period in 2020.
Net loss attributable to ordinary shareholders for the full year 2021 was RMB $453 7 million or U S dollar of $71 2 million.
Compared to RMB $274 6 million for the same period in 2020.
Dr. Kevin Xie: Research and development expenses for the fourth quarter were RMB $107.6 million. For U.S. dollars, 16.9 minutes, that comes here to RMB 60.7 minutes for the same period in 2020. The school year ended December 31, 2021, Research and Development Expenses for RMB 326.9 million, for US dollar 51.3 minutes, compared to RMB 168.8 million for the same period in 2020. These increases will prepare you to increase spending, to advance our early and clinical pipeline, higher headcounts, and increased expenses in share-based compensation.
Research and development expenses for the fourth quarter were RMB $107 6 million.
Our U S dollar $16 9 million as compared to RMB 67 minutes for the same period in 2020.
For the full year ended December 31 2021.
Research and development expenses were RMB $326 9 million.
Our U S dollar $51 3 million.
Care to RMB $168 8 million for the same period in 2020.
Increases were primarily due to increased spending.
Vance are already and the premium for pipelines.
Our head count and increased expenses and share based compensation.
Dr. Kevin Xie: Administrative expenses for the first quarter of RMB 32 million, for US dollar 5 million, compared to RMB 24.8 million for the same period in 2020. For the full year, Administrative expenses of RMB 137 million, or US dollar 21.5 million, as compared to RMB 45.6 million in 20.
Administrative expenses for the fourth quarter were RMB $32 million or U S dollar five minutes.
Compared to RMB $24 8 million for the same period in 2020.
For the full year and administrative expenses were RMB 137 million or <unk> $21 5 million.
Compared to RMB $45 6 million in 'twenty one.
Dr. William Tsao: The [inaudible] increases were primarily driven by an increase in recognition of share-based compensation expenses, as well as an expansion of an administrative function. With that, I'll turn the call back to Winn. Thank you, Kevin. Again, we are very pleased with our progress across our pipeline. Looking forward this year, we expect to build on our record of achievement. We have an active year of milestones ahead. Three areas of focus this year encompass the following
Increases were primarily driven by increased recognition of share based compensation expenses as well as expansion of and administrative functions.
With that I will turn the call back to winning.
Thank you Kevin.
Again, we are very pleased with our progress across our pipeline.
Looking forward this year, we expect to build on our record of achievements, we have an active year of milestones ahead.
Dr. William Tsao: Our priorities continue to advance in the tech transfer process for 12F with our US CDMO, and now we expect to rely on the U.S. and China for relapse the refractory multiple phenomena in the second half, 2022.
Key areas of focus this year encompass to fall.
Our priorities continue advancing the tech transfer process or 12, five with our U S. CMO.
And now we expect to file an IND in the U S and China for relapsed and refractory multiple myeloma.
In the second half 2022.
Dr. William Tsao: 2022. Concurrently, we are continuing to enroll patients in the Phase I RIT studies in China for 12F in RRMM and BNHL. And also are extending to early-line multiple myeloma. We plan to submit clinical updates on these studies to major medical conferences this year. For the true UCATI platform, we plan to present early-first human data from an IIT study underway for GC502 in adult patients with BAL at AACR in April. We are nearing the completion of enrollment, which we are studying for TC027 in patients with p-cell leukemia. We're also on track to commence the phase two portion of the registration phase 1-2 clinical trial for GC 007G that is underway in China.
Concurrently we are continuing to enroll patients in our phase one studies in China for 12 five.
And then in the B NHL and in also.
Extending too early line multiple myeloma.
We plan to submit clinical updates on these studies two major medical conferences this year.
While the <unk> platform with.
We plan to present early first in human data from <unk> study underway for GC firewall true.
Patients.
With B <unk> L at ACR in April .
We are nearing the completion of enrolment HD study with <unk> 27 in patients with T cell leukemia.
We're also on track to commence the phase II portion in 2022 of the registration phase.
One two clinical trial for GC doubled seven G that is underway in China.
Dr. William Tsao: Finally, under the smart car platform, we also anticipate to commence enrolling in the China RIT study for GC503 in metastatic positive solid tumors, including ovarian cancer, in 2022. In addition, we also plan to provide clinical data updates on current and new programs at major medical conferences, all published in Leith Journal. With that, I'd like to turn it back to the operator to open the session for your questions. Obradov.
Finally under the Smart car platform. We also anticipate two converged enrolling in the China study for GC <unk> III <unk> billing positive solid tumors, including ovarian cancer. In 2022. In addition, we also plan to provide clean.
Good data updates on current and new programs and a major medical conferences.
All published in lead journals.
With that I'd like to turn it back to the operator to open the session for your questions.
Operator.
Operator: If you'd like to ask a question, please press star, then 1. If your question hasn't been answered and you'd like to remove yourself from the queue, press the pound key. Our first question comes from Joe Catanzaro with Piper Sandler. Your line is open. Hey, guys.
If you'd like to ask a question. Please press Star then one if your question has been answered and you'd like to leave yourself. The Q press the pound key.
Our first question comes from Joe Catanzaro with Piper Sandler Your line is open.
Hey, guys. Thanks, so much for taking my questions here, maybe the first one from me I understand that your CMO has had some capacity constraints and William I think you may have alluded to this but wondering if there had been any GMP runs and whether there's anything you could say around comparability at this point between.
Joseph Catanzaro: Thanks so much for taking my questions here. Maybe the first one from me, I understand that your CDMO has had some capacity constraints. William, I think you may have alluded to this, but wondering if there have been any GMP runs and whether there's anything you could say around comparability at this point between the product being manufactured at the CDMO versus what was manufactured for the China IIT.
The product being manufactured at the CMO versus what was manufactured for the China.
Dr. William Tsao: Thanks, and I have a follow-up. Okay, I'm going to take that question. And Martina, feel free to jump in. Well, the manufactured capacity right now in the whole industry is in high demand, right? Adjustments were needed based on the kind of competitive situation.
Thanks, and I have a follow up.
Okay.
Take that question.
And it <unk> feel free to jump in.
Well manufacturer capacity right now you're seeing the flooring industry is in the high demand adjustments where needed based on kind of competitive situation. So there is no nothing to do with technical and expect a detective pods, including.
Dr. William Tsao: So there is nothing to do with the technical aspect. The technical part, including, you know, the tech transfer, the trial runs, the SOP, the trainings, is all good, all smooth. So it's simply a small logistical issue. Matina, do you have anything to add, or is it good?
The tech transfer.
Trial runs.
Okay Sop training is all good smooth so simply.
Logistic.
Small issue.
That's all I can say.
Hum.
But in Montana do you have anything to add.
It's good.
Dr. Martina Search: No, the complete picture. Thank you, William. Okay, I got it. That is helpful. And then another question, maybe, as well as that William you may have mentioned. But for GCO-12F's ongoing China IIT study, can you remind us of the myeloma cohorts that are currently enrolling in terms of line of therapy and whether there are any expectations to report updated clinical data from that trial sometime this year? Thank you. So that's certainly Martina's question.
Now complete picture. Thank you William.
Okay got it thanks.
And then another question maybe something.
As well that William you May have mentioned, but for <unk> ongoing China study can you remind us of the myeloma cohorts that are currently enrolling in terms of line of therapy and whether there are any expectations to report updated clinical data from that trial sometime this year. Thanks.
Sure.
Latinos question.
Dr. Martina Search: Yeah, sure. Thank you. Great question.
Yeah sure. Thank you great question, Yeah, we have been continuing enrolling patients that are relapsed refractory multiple myeloma study and we certainly planning on showing the data this year.
Dr. Martina Search: Yeah, we have been continuing and rolling patients in our left refractory multiple myeloma study, and we are certainly planning on showing the data this year. Once acceptance is clear at the conferences, we will also issue a press release for approval. So you can, you know, look forward to that data. And for lines of therapy, we already talked about that we are moving into, into, into earlier lines of therapy, and we are also planning on submitting that data once it is available to one of the major conferences. Okay, I got it, and I guess maybe if I could just squeeze one left, something more technical.
<unk> acceptance as clear at the conferences, we will also issue a press release for acceptance. So you can look forward to that data and fault lines of therapy, we already talked about that we are moving in solar into earlier lines of therapies and we also planning on submitting that data.
Once available to one of the major conferences this year.
Okay got it and I guess, maybe if I could just squeeze one last one in.
Sort of more and more technical for <unk> 503 million can you elaborate a little bit on the approach and construct design that will allow you to take a tumor suppressive signal and translate that into a positive signal for T cell proliferation and persistence.
Dr. Martina Search: For GC503, maybe can you elaborate a little bit on the approach and construct design that will allow you to take a tumor suppressive signal and translate that into a positive signal for T-cell proliferation and persistence? I think you might mix it up with the smart CAR T and the true UCAR T platforms. In the true UCAR T platforms, we don't have a mechanism that can turn a suppressive molecule into a positive signal
I think.
Mixed up with the smartcard.
And the <unk> content platforms and the <unk> platforms.
We have a mechanism that can turn a suppressive molecule into positive.
Dr. Martina Search: And now, let me just elaborate how this 502, if you're referring, is based on a true UCAR T platform. True UCAR T typically would have two CARs, one targeting CD7, which is a pan-T NK marker. So the purpose of this CAR is to suppress allogeneic T and NK cells, which means from the patient to reject the cut.
And now let me just elaborate how this five O two if you're referring to.
Is based on true concept clinic film.
Truly ekati have typically.
Would have two cars one targeting.
<unk>, seven which is a PNT NK marker.
So the purpose of this call is to suppress allo genetic T and NK cell <unk> to from the patient.
To reject the car T cells, so allo rejection from patient <unk> 10-K.
Dr. Martina Search: So allele rejection from patient T and NK could be detrimental to the CAR T cells' persistence and proliferation, so the CD7 car is designed to prevent that. The second car is really the tumor engine targeting car. In this case, the CD19, the GC502 is the best example to illustrate how this true CAR-T platform works. So the two cars work in the way that I just described.
It could be detrimental to the car T cell persistence and proliferation.
<unk> seven is designed to prevent that.
The second is really the tumor antigen targeting.
Targeting come.
In this case as CD 19.
The city from.
The <unk> two is the best example.
To illustrate this through car T platform works, so that <unk> work.
In a way that I just described now the 502 is targeting CD 19, and now. This example, really demonstrate the wide applicability by switching CD 19, two other tumor antigens for example, <unk>.
Dr. Martina Search: Now, this 502 is targeting CD19, and this example really demonstrates the wide applicability by switching CD19 to other tumor antigens, for example, BCMA, any that are known CAR-T tumor targets.
It.
The known car T.
Tumor target.
Dr. Martina Search: So there is also an enhancer embedded in this Yucati platform to facilitate the Yucati to proliferate and survive in the hostile environment. I hope I explained it well. Yeah, no, that's helpful. I guess I was asking about GT503. Apologies if I missed the boat, but we could maybe follow up on that offline.
So that.
There is also an enhancer embedded industry with kind of your platform to facilitate that youll continue to proliferate and the persistence in the hostile environment.
I hope I explained it well.
Yes.
Well I guess I was asking about <unk> III apologies, if I, if I missed it but we could maybe find okay. We can follow up on that offline. Okay. Thanks, so much William.
Alright, thank you.
Joseph Catanzaro: All right, thank you. Our next question comes from Kelly Xie with Jeffries. Your line is open. Hi, good morning. This is Dave on behalf of Kalishi.
Our next question comes from Kelly <unk> with Jefferies. Your line is open.
Kelly Xie: Just a few questions. One is regarding 012F in BNHL. So, should we expect any data this year? Or do you want to see a better one?
Hi, Good morning, this is Dave on for Caliche.
Two questions.
One is regarding.
Zero to Atlas and <unk>.
So should we expect any data this year.
But now you want to see that one.
Dr. Martina Search: Yes, you should, Okay, and another one is for your upcoming presentation at AACR. Any color on, like, number of patients? Data on the... at the ACR. Should I do it, William?
Yes, you should.
Okay.
Another one is a part of.
Coming presentation at ACR.
Any color on like number of patients.
Data.
On the.
At the ACR.
Should I William.
Yes.
Thank you for questions. Please take it yes. Thank you Doug.
Dr. William Tsao: Yeah. Yeah. Questions, please. Take it.
Dr. Martina Search: Yeah. Yeah, so ACS, you know, the abstract is still not out yet. So we can't give you any hint here. But it's not going to be very long, you know, April, beginning of April.
Yeah. So as you know the abstract is still not out yet so we can't give you any hint here, but it's not going to be very long you know April beginning of April ACR. So please hold on tight and Youll see the data.
Dr. Martina Search: So please hold on tight, and you will see the data. All right, sounds good. Thank you. Thank you. Our next question comes from Nick Abbott with Wells Fargo. Your line is open.
Alright that sounds good thank you.
Thank you.
Our next question comes from Nick Abbott with Wells Fargo. Your line is open.
Nick Abbott: Terrific. Thanks. Good morning.
Terrific. Thanks, good morning.
No prepared remarks.
<unk> indicated that two <unk>.
<unk> expression on T cells.
Nick Abbott: In your prepared remarks, William, you indicated that, you know, PCMA expression on B-cells ranges widely; I think the lower end was 39%. So my first question is, can you talk about where in the BCL developmental lineage BCMAs express, what controls it, and are you able to modulate that?
Ranges widely I think the lower end was 39%.
So my first question is.
Can you talk about the weather.
T cell developmental lineage <unk> express will controls it.
Nick Abbott: Would you, for example, pre-treat the patient with something that increases BCMA expression prior to fatigue? Yeah, that's an interesting approach. I haven't thought about causing BCMA expression on NHL. But, you know, this is our kind of philosophy.
Are you able to modulate that equally would you able to speak for example.
Pre treat the patient with something that increases <unk> <unk> expression.
<unk> two car T treatment.
Yes.
It's an interesting.
Approach I haven't thought about it.
To induce <unk> expression on NHL, but.
This is our kind of philosophy, we want to utilize the power of us so not to give additional quote help to complicate the matter.
As a as.
Dr. William Tsao: We want to utilize the power of a cell, not to give additional quote, quote, quote, help to complicate the matter. As a representative of companies on the team, we strongly believe the T-cell has enough power. All you need to do is, you know, release the power without causing trouble.
As a representative of the company's R&D team, we strongly believe the T cell has enough power only need to do is.
To read.
Two leash.
The power without causing trouble now the two year comp design is exactly one of the key design or the feature is to not include combination therapy.
Dr. William Tsao: Now, the two-U card design is exactly one of the key designs, or the feature is to not include combination therapy. So preconditioning, if it's easy, and the drug is safe, it, you know, can be PK wise, can really help expression of BCMA in NHL. There might be, you know, practical applications. And in our case, it's like any other potential tumor marker. The expression level doesn't have to be very high, as long as it's there.
So pre condition.
Easy and it's a drug is safe.
Can be PK wise can really help expression or be CMA on NHL.
B practical and in our case.
It's like any other.
Potential tumor markers.
Oppression level doesn't have to be very high as long as they're now the data shows 39% to 90% but.
Dr. William Tsao: Now, the data shows 39% to 90%, but the methodology behind this data might be classical IHC or flow cytometry, which are all based on antibody binding. And then we know the antibody binding assays are not as sensitive as CAR T. CAR T is 1,000 times more sensitive, so we suspect. In those patients with lower BCMA expression, it doesn't mean they are not there, but they're just very faintly expressed. It's like CD-19 on multiple myeloma. They are there, but they are weakly expressed, but a car T can pick them up.
The domestic knowledge behind this data might be classical.
I would see a flow cytometry, which all based on antibody findings and then we know the antibody binding assays are not as sensitive as car T car T is 1000 times higher so we suspect.
In those patients with lower <unk> expression. It doesn't mean, they're not there, but they're just very faintly expressed.
It's like CD 19 or multiple myeloma.
Yeah, but weekly expressed but a car T. You can pick it up.
Nick Abbott: So we don't have this exclusion criteria saying that if the NHL patient has no BCMA expression, we'll exclude them. No, we don't do that. So at this moment, the dual targeting is going to help the CAR-T to pick it up, the NHL, that makes a lot of sense. You know, as you think about going forward with... and the BCMA franchise. You know, how do you think about having a third car, so a CD7 car? So, combining the SARS-CoV-2 U-Car platform, what are the considerations about having three cars? That's a very deep question, Nick.
No.
We don't have this inclusion exclusion criteria, saying.
If the NHL patients has no <unk> expression will exclude them, we don't do that so at this moment.
<unk> targeting is going to help too for the car T to pick it up and it yourselves.
Perfect. Thank you Dan.
Makes a lot of sense.
And as you think about going forward with the.
The <unk> franchise.
<unk>.
How do you think about adding a third the cost of a CD seven call.
So combining the two.
The floor is covered through Yuko platform what are the considerations about.
Pressing three cars.
That's fair.
Very deep question Nick.
Yeah.
Dr. William Tsao: So, you know, this is actually a very intriguing question. I have to say, it's kind of in our consideration, but I cannot review it anymore. It is, you know, one of the interesting ideas. But I think the key question here is really about the CM.
This is actually very intriguing questions.
I have to say we are.
It's kind of in our consideration, but I cannot review anymore.
It is one of the.
Interesting idea, but I think the key question here is it really the CMC.
Dr. William Tsao: We have ample experience with dual-chi and dual-chi expressions and, especially the CMC, so I can't give a clear answer at the moment, but I think that's an interesting thought. Okay, thanks. And then, just last one for me, you have a Claudin smart car listed.
We have ample experience with fewer clients in tok expressions.
Especially the CMC so.
I can't give a.
Clear answer at the moment, but I think that the interest income.
Okay. Thanks, and then just last one for me you have quoted smoker listed.
Nick Abbott: Is that expected to go into the clinic in China, or is the goal to get it into the clinic in China this year as well? Yes, it's going to clinical in China this year. It's our de-risk strategy.
Is that expected to go into the clinic in China or is the goal to get it in the clinic in China This year as well.
Yes.
Going to clinical in China This year.
It's our.
Derisk strategy.
Nick Abbott: Great reporter. See you at AACR, hopefully. Thank you. Thank you. Looking forward to it. Our next question comes from Justin Zelin with the TIG. Your line is open. Hi, thanks for taking the question, team. Just a quick one.
Great look forward to seeing you at ACR hopefully thank you.
Okay. Thank you looking forward.
Our next question comes from Jeff <unk> with <unk>. Your line is open.
Hi, Thanks for taking the question team.
Just a quick one.
Justin Zelin: We recently saw approval for Legend J&J's Curvicti Siltacel, which I believe was the first FDA-approved Chinese developed CAR-T. Just wondering if you see any readthroughs to Gracell and your pipeline, and your strategy. Thank you. I think it's a good question for you, Martina. Sure. So this time, it was expected that Kavikti was going to get approval. We already consider that this is part of a huge amount of BCMA-only targeted products out there. There are many out there, so we differentiate not only by being dual targeting but also by the fastening section.
We saw approval for religion J&J is.
Kervick T cell to cell I believe it was the first.
SBA approved trying to develop car T. You just wondering if you see any read throughs to Grace Allen and your pipeline your strategy.
<unk>.
Yes, I think it's.
Martina I think.
Good question for you.
Sure.
So it was expected that he is going to get approval.
We already consider that this is a part of a huge amount of PCA may only targeted products. There are many out there. So we differentiate it not only but being dual targeting but also the fast any spectrum.
Dr. Martina Search: So at this point in time, this is our strategy, and there is no need to just. Great, thank you for taking the questions. There are no further questions.
So at this point in time. This is a solid strategy and there is no need to adjust.
Great. Thank you for taking the question.
Sure you're welcome.
Dr. William Tsao: I'd like to turn the call back over to Dr. William Chow for closing remarks. Thank you again to everyone for joining us on the call. The Gracell team is very proud of what we have accomplished over the last five years since our founding. We have rapidly expanded our teams in China and the U.S. with exceptional talent. We have advanced many clinical programs and de-risked others through clinical investigator-initiated trials in China, while also expanding our manufacturing facilities to support our extensive pipeline.
There are no further questions I'd like to turn the call back over to Dr. William Zhao for closing remarks.
Thank you again to everyone for joining us on our call.
Dr. William Tsao: To support our R&D efforts, we continue to form new external partnerships and expand our internal manufacturing capability. In conclusion, Gracell is well positioned to advance clinical developments of breakthrough CAR T cell therapy that has the potential to overcome key challenges by leveraging our proprietary fast car, true-you car, and smart car technology plans.
So a great sales team is very proud of what we have accomplished over the last five years since our founding.
Operator: We look forward to further advancing our clinical programs, and we will keep everyone updated along the way. Thank you. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect. Outro Music
We have rapidly expand our teams in China, and the U S with exceptional talent.
We have an advanced many clinical programs and de risk others through clinical investigator initiated trials in China.
While also expanding our manufacturing facilities to support our extensive pipeline.
To support our R&D efforts, we continue to form new external partnerships.
And expand our internal manufacturing capabilities.
In conclusion, <unk> is well positioned to advanced clinical developments a breakthrough.
T cell therapies.
Have the potential to overcome key challenges by leveraging our proprietary <unk> com <unk> com and a small currency technology platforms.
We look forward to further advancing our clinical programs and it will keep everyone updated along the way.
Thank you.
Ladies and gentlemen. This concludes today's presentation. Thank you once again for your participation you may now disconnect.
[music].
Yes.