Gamida Cell Ltd (GMDA) 2021 Q4 法說會逐字稿

Thank you for standing by. Welcome to Gamida Cell's conference call for the fourth quarter and full-year 2021 financial results. My name is Howard, and I'll be your operator for today's call. Please be advised that this call is being recorded at Gamida Cell's request. Now I would like to introduce your host for today's conference, Heather DiVecchia, Gamida Cell's Chief of Staff. Please go ahead.

Thank you, Howard. And good morning, everyone. Welcome to today's call, during which we will provide an update on the company and review our financial results for the fourth quarter and full year of 2021. Earlier this morning, we issued a press release summarizing our financial results and progress across the company, which is available on our website at www.gamidacell.com (sic - see official Gamida Cell website, "www.gamida-cell.com").

Here with me on our call today are Julian Adams, Chief Executive Officer; Ronit Simantov, our Chief Medical Officer and Chief Scientific Officer; Michele Korfin, our Chief Operating Officer and Chief Commercial Officer; and Shai Lankry, Chief Financial Officer.

During this call, we may make forward-looking statements about our future expectations and plans, including in respect to the timing of initiation and progress of, and data reported from the clinical trials of our product candidates; anticipated regulatory filings, including the submission of the BLA for omidubicel to the FDA; commercialization planning efforts; the potentially life-saving or curative therapeutic and commercial potential of omidubicel; and our expectations regarding our projected cash to be used for operating activities and cash runway.

Our actual results may differ materially from what we project today due to a number of important factors, including the impact of COVID-19 pandemic on our operations; the scope, progress, and expansion of our clinical trials and cost impact thereof; clinical, scientific, regulatory, and technical development; and those inherent in the process of developing and commercializing product candidates that are safe and effective for use as human therapeutics; and the endeavor of building a business around such product candidates as well as those considerations described in the Risk Factors section of our most recent annual report on Form 20-F and other filings that we make with the SEC from time to time.

These forward-looking statements represent our views only as of today, and we caution you that we may not update them in the future, whether as a result of new information, future events, or otherwise. Now I'd like to turn the call over to Julian.

Thank you, Heather, and thanks to everyone for joining us this morning. Before I begin, I want to take a moment to acknowledge the major events in the Ukraine that are impacting the world globally over the past few weeks. While we don't have any operations in the Ukraine or Russia and expect minimal impact to our operations, as global citizens, our thoughts are with all those affected.

At Gamida Cell, we are incredibly proud to be part of the significant advancements occurring in the field of cell therapy as it continues to grow and progress towards cures for patients in need. 2021 was an important year for us as we progressed our two clinical-stage, NAM-enabled cell therapy programs, omidubicel and GDA-201, both of which holds significant potential to benefit patients suffering from hematologic malignancies and serious blood disorders. Additionally, we further expanded our NAM-enabled platform with the addition of genetically modified NAM-enabled NK cell constructs, allowing us to leverage our expertise in NK cells to potentially treat various hematologic malignancies and solid tumors.

I will start today's call by commenting on our lead program, omidubicel, which has breakthrough therapy designation and the potential to be the first FDA-approved cell therapy for stem-cell transplant. Throughout 2021, we announced several data presentations which contribute to the evidence for omidubicel's potential efficacy and also the positive health economic impact of omidubicel, with data demonstrating a reduction in healthcare resource utilization.

As Ronit will describe later on in this call, this reduction in healthcare resource utilization is very important for patients, hospitals, and payers. The robust data that we have generated in support of the potential for omidubicel led us to our most recent and exciting milestone last month, namely the initiation of the rolling BLA for omidubicel with the submission of our nonclinical module following the receipt -- the recent receipt of positive CMC-focused Type B meeting correspondence from the FDA.

In this correspondence, the FDA confirmed analytical comparability between our wholly owned commercial manufacturing facility in Israel to the omidubicel batches that were produced at the clinical manufacturing sites for the Phase 3 study. This month, we also submitted our clinical module to the FDA. We are on track to submit the remaining modules and to complete -- and complete the full BLA submission by the end of the second quarter. We are thrilled to have reached this inflection point and look forward to working with the FDA to bring omidubicel to patients as soon as possible.

Beyond omidubicel, we are also developing our NAM-enabled NK cell pipeline, which is led by GDA-201. GDA-201 leverages our proprietary NAM technology platform to expand natural killer cells to enhance the functionality, direct tumor-cell-killing properties, and antibody-dependent cellular cytotoxicity or ADCC. We are highly encouraged by the potential of GDA-201, which has produced truly remarkable results in a Phase 1 investigator-sponsored study where we have seen very high and complete durable responses in both follicular lymphoma and diffuse large B-cell lymphoma.

In September 2021, we submitted an IND application to the FDA for a Phase 1/2 trial with a cryopreserved formulation of GDA-201 in patients with diffuse large B-cell lymphoma and follicular lymphoma. Following the submission, we were placed on clinical hold in November of '21 prior to patients being dosed since the FDA had questions about donor eligibility procedures and assay qualification. We are actively working with the FDA to address their comments to enable an IND acceptance and study initiation. This year, we plan to initiate dosing in this Phase 1/2 study.

Moving to our newest product candidates, our genetically modified NAM NK-enabled cell therapy programs. Last year, we were excited to establish a broad pipeline of NK product candidates that utilize CAR- and CRISPR-mediated strategies to increase targeting potency and persistence against hematologic malignancies and solid tumors. Robust preclinical evidence gives us the confidence that these new NAM-enabled NK product candidates hold promise as potentially curative therapies for both hematologic cancers and solid tumors.

Furthermore, we announced a research collaboration with the Dana-Farber Cancer Institute for GDA-601, a CD38 CRISPR knockout combined with a CD38 CAR NK cell construct that has demonstrated promising preclinical results against multiple myeloma cell lines. We are excited to leverage the expertise of researchers at Dana-Farber to study the in vitro NK-cell killing activity of GDA-601 in multiple myeloma. Throughout 2022, we plan to execute preclinical proof-of-concept studies for these genetically modified NK therapeutic targets. And by the end of 2022, select a pipeline candidate for IND-enabling studies.

With the progress we achieved in 2021, we are encouraged about what the future holds for Gamida Cell in '22. And of course, this wouldn't be possible without our employees, whose dedication is focused on advancing therapies to help address unmet needs for patients. I am grateful for and proud of their continued determination and focus on patience, which has brought us to where we are today.

Before turning the call over to Ronit, I would like to take a moment to congratulate her on her recent promotion, now assuming the role of not only Chief Medical Officer but also Chief Scientific Officer. We at Gamida thank you all for your contributions thus far and look forward to your continued work towards division with your expanded role. Ronit?

Thanks, Julian. And good morning, everyone. Thank you for joining us on our call. In 2021, we had the opportunity to present a broad range of scientific and clinical data on omidubicel, tying together preclinical and translational analyses with clinical data, patient experience, long-term outcomes, and value to the healthcare system.

In preclinical presentations in 2021, we demonstrated that our nicotinamide or NAM platform generates a unique cellular phenotype through modulation of metabolic pathways, leading to highly functional and potent stem cells. In translational data, we showed that patients treated with omidubicel have robust functional reconstitution of T- and B-cell subsets, dendritic cells, and natural killer cells in the days and weeks following transplant.

The translational data provided mechanistic support for the clinical results of our global Phase 3 randomized trial, the results of which were published in October 2021, demonstrating rapid hematopoietic recovery, significantly decreased infections, and shorter duration of hospitalization for patients transplanted with omidubicel. Of note, the patients in our clinical trial were in critical need of allogeneic transplant for hematologic malignancies with few or no alternatives available.

Looking back at the totality of our experience with omidubicel, we presented follow-up data from over 10 years of clinical studies, demonstrating long-term sustainable hematopoiesis and immune competence in patients. We then went on to show that omidubicel could decrease the cost to the healthcare system as patients treated with omidubicel had reduced healthcare resource utilization, including blood transfusion, outpatient procedures, and time in intensive care units.

At next month's Transplantation and Cellular Therapy Meetings in Salt Lake City, we have eight abstracts accepted and plan to report new data focused on patient outcomes and health-related quality of life. Taken together, we have continued to add to the body of evidence supporting the mechanism of action, clinical activity, patient experience, and value of omidubicel as a potential life-saving therapy. Moreover, we are confident in the scientific and clinical package we have assembled and our efforts to make omidubicel available to patients in need of a hematopoietic stem cell transplant.

We also made considerable progress in our NAM-based natural killer cell platform. We presented preclinical data characterizing the properties of GDA-201. We showed that NAM mediates a set of cellular processes expanding NK cells while down-regulating differentiation, cellular stress, and exhaustion pathways that are typically activated in culture. GDA-201 cells are characterized by a rejuvenated NK phenotype similar to cytokine-induced memory-like NK cells and was shown to be highly cytotoxic in in vitro and in vivo assays.

These findings were supported by the clinical data reported in the Phase 1 investigator-sponsored study at the University of Minnesota. At ASH, we presented two-year follow-up data in patients with non-Hodgkin lymphoma, showing an overall response rate of 74%, including 13 out of 14 complete responses with a median duration of response of 16 months, 78% overall survival, and toxicities in line with those reported previously for GDA-201. We've now developed the cryopreserved formulation and plan to initiate a multicenter company-sponsored study this year in patients with follicular lymphoma and diffuse large B-cell lymphoma.

In addition, we reported that we've expanded upon our NAM platform to develop genetically modified NK cells in GDA-301, GDA-501, and GDA-601, each of which is proceeding with preclinical proof-of-concept studies as we advance towards IND-enabling studies. Overall, 2021 was a tremendously productive year in research and development and clinical research. We look towards continuing to validate the therapeutic potential of our product candidate. I will now turn the call over to Michele, who will talk more about our launch readiness for omidubicel. Michele?

Thank you, Ronit. And good morning, everyone. This year has started off strong already as last month, we initiated our rolling BLA submission for omidubicel. We continue to make excellent progress advancing our Gamida-owned manufacturing facility in Israel. The FDA acknowledgment of the analytical comparability from our planned Gamida commercial facility as compared to the facility used for the Phase 3 study was an important milestone as we work toward advancing omidubicel. The commercial opportunity for omidubicel is extremely encouraging based on our continued assessment of market insights, and we continue to focus on our commercial preparation.

In parallel with our rolling BLA submission, we are additionally assessing strategic alternatives for the potential commercialization of omidubicel, including, potentially, partnerships to expand the reach of omidubicel. Omidubicel has the potential to be the first FDA-approved advanced cell therapy product for allogeneic stem cell transplant in patients with hematologic malignancies.

For patients with hematologic malignancies that are deemed eligible for an allogeneic stem cell transplant, the procedure is their best chance for a potential cure. In the US, there are approximately 8,000 patients above the age of 12 with hematologic malignancies who undergo an allogeneic stem cell transplant each year. Unfortunately though, there are approximately 1,200 patients each year who are also aged 12 and up with hematologic malignancies who are deemed eligible for an allogeneic stem cell transplant but cannot find an appropriate donor.

Unfortunately, we observe racial disparity in the US in regard to access to allogeneic stem cell transplants. If you are non-Caucasian and do not have access to a family member donor, you have a very low likelihood of a finding a match in the public database. For example, patients who are African American may only have about a 20% chance of finding a match. For patients in need of a stem cell transplant, this is often their only chance for a cure. We are diligently working to advance omidubicel and to expand access to patients.

Based on encouraging clinical data and the less-stringent matching criteria, transplanter feedback indicates that omidubicel has the potential to improve outcomes for allogeneic stem cell transplant patients compared to other donor sources and expand access for patients who cannot find a suitable donor. In the US, there are approximately 200 transplant centers that perform allogeneic stem cell transplants. 70 of those centers conduct about 80% of the transplants, and our medical team continues to engage with those top 70 centers through one-on-one meetings and at medical conferences.

We also continue to assess market insights from transplanters in the US. Based on extensive market research, we see the potential for omidubicel to treat approximately 2,000 to 2,500 patients per year upon reaching peak market share. This equates to approximately 20% to 25% market share of the addressable population. Our market access team is also actively engaging meetings with national and regional commercial payers, and the feedback continues to be very encouraging. Payers recognize the overall value proposition, including the strength of the omidubicel clinical data and the health economic data we have published to date.

In summary, we are excited by the potential of omidubicel to be the first FDA-approved cell therapy for allogeneic stem cell transplant, and we are also encouraged by the clinical data and feedback from physicians and payers. I will now turn the call over to Shai to review our financial results.

Thank you, Michele. And good morning, everyone. Today, I will summarize our financial results for the full year of 2021. As of December 31, 2021, our total cash position was approximately $96 million compared to $127.2 million as of December 31 of last year. Research and development expenses for the year were $50.2 million compared to $38.9 million for the same period in 2020. The increase was primarily due to a $5.4 million increase in omidubicel commercial manufacturing readiness activities and the advancement of our NK programs, as well as an increase of $5.9 million in broadening our scientific capabilities and talent.

Commercial expenses in 2021 were $20 million compared to $8.9 million in 2020. The increase was mainly due to a $6.5 million increase in commercial readiness expenses and a $4.6 million increase in headcount within our commercial organization. Going forward, we anticipate reducing our near-term commercial readiness expenses as we are assessing alternative for the commercialization of omidubicel, including potential US or global partnerships.

General and administrative expenses were $17 million in 2021 compared to $13.2 million in 2020. The increase was mainly due to a $2.6 million increase in professional services expenses and a $1.2 million increase in headcount and related expenses. Finance expenses, net, were $2.6 million in 2021 compared to $0.6 million in 2020. The increase was primarily due to a $4.4 million interest expenses from our convertible note offset by a $2.1 million capitalization in other non-cash income and a $0.2 million increase in interest income from cash management.

Net loss in 2021 was $89.8 million compared to a net loss of $61.6 million in 2020. We continue to expect cash use for ongoing operating activity this year to range from $60 to $70 million. We anticipate that our current total cash position will support our ongoing operating activities into mid-2023. This cash runway guidance is based on our current operational plans and excludes any additional funding that may be received or business development activities that may be undertaken. I will now turn the call back over to Julian.

Thank you, Shai. As we look ahead into what we have set up to accomplish in this year, 2022, I believe we are well positioned to deliver on our mission of developing potentially curative cell therapies for patients with blood cancers, solid tumors, and other serious blood disorders. We look towards our full BLA submission for omidubicel expected in the second quarter of this year and the planned initiation of our Phase 1/2 multi-centered Gamida Cell-sponsored study for GDA-201 in non-Hodgkin lymphoma.

We are excited for the opportunity to continue leveraging our unique NAM-enabled platform across a broad range of cell therapies, and I look forward to providing updates throughout the year. Now, we will open the call for questions. Operator?

(Operator Instructions) Jonathan Miller, Evercore ISI.

Hey, guys. Thanks for taking my questions. First, maybe on GDA-201, it feels like the language here seems a little bit similar to last update, and I just wondered if you had any additional color on your recent interactions with the agency and what your current thoughts are on the ability to get that IND [quickly]? And then maybe, secondly, I'm happy to see the runway guidance reinstated but just wanted to get some clarity. How much commercial prep is included in the current runway guidance, and maybe, how much clinical work for GDA-201 is included in that clinical guidance?

So let me begin by addressing your first part of your question. We haven't had any direct communication with the FDA. The FDA provided absolute clarity on what issues we needed to resolve. Most of those issues are resolved, and we are getting ready to resubmit the amendment to the IND, and we'll be announcing when the IND is accepted. Regarding runway guidance, let me turn it over to Michele and Shai to talk about launch readiness and a use of cash for support of GDA-201. Michele?

Thank you, Julian, and good morning, Jonathan. So, Jonathan, I'll start, and then I'll turn to Shai for the additional financials.

So in regard to runway guidance -- so for 2021, we were able to complete a lot of the key milestones for commercial preparation that led to the increase that Shai discussed for OpEx. So some of those included the market insights such as quantitative assessments from transplanters and feedback from payers. In addition, a very, very important milestone for us in 2021 was the readiness of Gamida Cell Assist.

Although Gamida Cell Assist fits within the commercial organization, it plays a critical role in starting the chain of identity and monitoring the chain of identity and chain of custody. Although omidubicel has a less-stringent requirement, it is still an individualized therapy. And hence, we need to demonstrate chain of identity, chain of custody.

That key work for Gamida Cell Assist, including building the team, developing the processes, and establishing the IT infrastructure was all completed in 2021. So what that allowed us to do in 2022, as we are assessing our strategic alternatives or potential strategic alternatives for launch, it allowed us to decrease the spend in regard to some of the commercial preparation because of the fact that so much had been done in '21. So let me turn to Shai to give us the actual financial details. And then, Jonathan, we'll see if you have any follow-up questions.

Thank you, Michele. So, Jonathan, for your question, I would divide the answer into two. As Michele alluded for the commercial, we did an internal robust process of prioritization our expense in 2022 in order to meet the cash runway guidance. And I can tell you that all the critical activity will continue to be advanced. In addition, as we mentioned in the previous comments, we did reduce some of the spending, which are less critical for the next few months.

As for the R&D GDA-201 in particular, I can assure you that we continue to advance the GDA-201. As part of the prioritization, we didn't reduce any of the GDA-201. We continued to advance this program, including the potential initiation of trial later this year and first patient in.

Thanks so much, guys. [No more questions].

Thank you, Jon.

Thank you. Ed Tenthoff, Piper Sandler.

Great. Thank you very much. And good morning, everybody. So I wanted to dig in a little bit more to the considerations with respect to omidubicel marketing. To me, it seems like the greatest value would be routine if this is a therapy that you take to market yourself. But can you give us a little bit more just in terms of how you're assessing this? Could this be overseas deal where you keep the US? Could this be some global deal? Give us maybe a sense for how and what kinds of options you're considering. Thanks.

So Ed, thank you for your question, and good morning. As was mentioned in the script, we're assessing our strategic alternatives for omidubicel, and that's driven by our desire to see as many patients as possible gain access to omidubicel. So we are discussing regional deals, potential regional deals, as well as potential US deals with partners that may have a unique interest in the hematology-oncology franchise and that pairs up with their portfolio, and already has significant infrastructure to be able to deliver omidubicel to as many patients as possible.

Our involvement will always be a very intimate because we are the manufacturer. And as you know, in cell therapies, the manufacturing facilities is critical to supporting any kind of commercial product. So we haven't made any choices yet, and we're starting -- and certainly, once the BLA is fully filed and accepted, that will open up avenues to conversations with interested parties.

That's very helpful, Julian. I appreciate that additional color.

My pleasure.

Thank you. Jason Butler, JMP Securities.

Hi. Thanks. For taking the question. Just another on omidubicel. Can you just talk about plans for additional data presentations this year, including from the open-label extension or expanded access program? Thank you.

So thank you, Jason, for your question. Ronit mentioned during the prepared remarks that we have eight abstracts at TCT. But maybe, Ronit, you could perhaps highlight other venues where we might present the maturing data set for omidubicel?

Absolutely. And thank you, Jason, for your question. So at TCT, as I mentioned, we'll be focusing on long-term follow-up information as well as patient-reported outcomes, health-related quality of life, additional immune reconstitution data and some preclinical data as well, and some information on the value and cost of care.

In terms of the expanded access program, we are continuing to recruit patients for the expanded access program. Have not made a definitive decision about what the appropriate time would be to present that growing a cohort of patients. But when there is a, I think, critical amount of information that's worth presenting, we certainly will do that, either by the end of the year at a hematologic meeting or maybe next year at the transplant meeting.

Great. Thank you.

Thank you. Gil Blum, Needham & Co.

Good morning, everyone, and thanks for taking our questions. So this one's for Michele. From your discussions with physicians, what feedback have you been getting regarding their interest in an FDA-approved transplant versus what they've been doing to date? The focus here being whether they have an opinion on something that is FDA approved and the feedback that you've heard so far.

Thank you, Gil, and good morning. We've done a lot of work speaking to physicians, and what is encouraging for them about omidubicel, which falls into the category of an FDA-approved therapy, is the following. So first off, Gamida Cell will take on the responsibility around chain of identity and chain of custody from the time of the patient selection from omidubicel all the way through the return of the therapy to the center. So that's an important responsibility, and that's something that comes with being an FDA-approved therapy.

The other aspect is around the omidubicel itself. So the NAM technology allows us to not only expand but enhance the cells, and some of the challenges associated with using other donor sources is to have an adequate number of cells. Does the donor potentially have some co-morbidities that could potentially be affecting the donor ability? So the fact with omidubicel that we will be sort of a FDA-regulated therapy with a defined threshold around release criteria, that is viewed as a positive.

Yeah, I will say consistently the feedback we hear from US transplanters is that when they see the omidubicel clinical data, they see omidubicel opportunity for their patients falling into two key categories. The first, from the physician's perspective, is the ability to improve outcomes as compared to donor sources that they're currently using. And then the second, that very critical one of those patients who are deemed eligible for transplant but can't find a match is a very important opportunity for omidubicel.

Given the fact we have a less-stringent matching criteria, we demonstrated in our clinical study we had approximately 40% of patients that were non-Caucasian in our clinical study. So those two key opportunities really do resonate consistently when we speak to physicians.

And if I may add, Michele, there's no question that having a quality-assured product with specifications and an FDA label clearly gives us the opportunity to engage with physicians and educate. And over time, this is an exercise in behavioral economics, if you will. If physicians find patients that are suitable for omidubicel and have a good experience, that will go a long way to encouraging them to continue to prescribe omidubicel. So we think that an FDA label for the first-ever sponsored randomized Phase 3 study is a significant game changer for the field of hematopoietic stem cell transplant.

Thank you, Michele. and thank you, Julian, for taking our questions.

Thank you, Gil.

Thank you, Gil.

Thank you. (Operator Instructions) Matthew Cross, Alliance Global.

Hi all. Good morning, and thanks for taking a couple of questions from me, both on the NK cell side. One, I wanted to ask regarding the cryopreservation status for GDA-201. I know you'd previously tested omidubicel as both a cryopreserved and non-cryopreserved product. So as you're finalizing these IND requirements with the FDA for 201, I was just hoping to get a recap on the clinical supply chain for that asset in terms of cold chain and what's required for that product in particular, given continuing supply issues at a broad level.

So let me take that on. The team has worked very diligently through 2021 to perfect and optimize the cryopreservation. We now have product and stability with many months of stability maintained at liquid nitrogen. So the goal of this is to have an off-the-shelf product to enable a multi-center Phase 1/2 study and be able to recruit patients with a single treatment with GDA-201. So all of those activities have been attended to, and we're just finalizing the amendment to the IND to resubmit to the FDA and begin the clinical study in 2022.

Got it. Okay. Thanks, Julian. Appreciate the confirmation there. And then you had stated that you're looking to select a candidate for IND-enabling studies this year at a genetically modified NK cell program. I just wanted to can confirm whether I'm taking that statement overly literally. Are you looking at advancing one of these four programs to [create] IND this year and tabling the rest for a bit? Or all of these making progress, and maybe just one will become a frontrunner during the year? Thanks.

So, Matt, thank you for your very important question. So right now, we have three candidates that are progressing. It's all data driven. And my comments about GDA-601 further allowed us to expand our collaboration with Dana-Farber to look at multiple myeloma cell lines as well as fresh patient isolates, who are patients who have been heavily pretreated. The idea is progress all three but select one candidate for IND-enabling studies and then subsequently continue to make progress on the other candidates. Again, it will all be data-driven, and we'll select the candidate with the most compelling data going forward.

Great. Okay. Thanks for the clarification there as well. I appreciate all the answers.

Thank you. I'm showing no additionals in the queue -- additional questions in the queue at this time. I'd like to turn the conference back over to Julian Adams for any closing remarks.

Thank you, operator. And thank you, everyone, for joining us on today's call. We look forward to engaging with you. And have a good day, everyone, and see you next quarter.

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day.