IGM Biosciences, Inc. (NASDAQ:IGMS) Q4 2022 Earnings Call Transcript

IGM Biosciences, Inc. (NASDAQ:IGMS) Q4 2022 Earnings Call Transcript March 31, 2023

Operator: Good day, everyone, and welcome to the IGM Biosciences’ Fourth Quarter and Full Year 2022 Financial Results and Corporate Update Call. Today’s call is being recorded. At this time, I would like to turn the call over to Fred Schwarzer, Chief Executive Officer of IGM.

Fred Schwarzer: Thank you, operator. And thanks to all of you joining us on this call. On behalf of IGM, I’m joined today by Misbah Tahir, Chief Financial Officer; Dr. Chris Takimoto, Chief Medical Officer; Dr. Bruce Keyt, Chief Scientific Officer; and Dr. Mary Beth Harler, President, IGM Autoimmunity and Inflammation. Please note that we will be making forward-looking statements on this call including statements about IGM’s plans, expectations and forecasts and about future events. Actual results may differ materially as a result of various risks and uncertainties including those discussed in the Company’s most recent annual report on Form 10-K as well as its other filings with the SEC. Any forward-looking statements represent IGM’s views as of today, March 30, 2023 only, and the Company disclaims any obligation to update these statements, except as required by law.

Following this call, a replay will be available on the Company’s website, www.igmbio.com. I would like to start with a few introductory remarks and then I will turn the call over to Misbah to take you through our 2022 financial results. After Misbah’s update, Chris will update you on clinical development of IGM-8444, our death receptor 5 agonist antibody. Next, Mary Beth will update you on our development plans for Imvotamab and autoimmune diseases. We will then turn it back over to Chris to discuss the two most recent product candidates in our oncology pipeline, IGM-7354, our IGM targeted immunostimulatory IL-15 cytokine; and IgM-2644, our CD38/CD3 T cell engager, a next generation CD38 antibody for multiple myeloma. Looking back, 2022 was a transformational year for IGM.

At the end of the first quarter, we entered into an important collaboration with Sanofi to develop novel IgM agonist antibodies to address three oncology targets and three autoimmune targets. Throughout the year we also continued the clinical development of our death receptor 5 agonist antibody, IGM-8444, particularly in combination with FOLFIRI for the treatment of colorectal cancer. We are very pleased with the data we have seen from those clinical development efforts as we announced in January of this year. These data have provided the basis for our decision to immediately move into a randomized study of IGM-8444 in second-line, metastatic, colorectal cancer in combination with FOLFIRI and bevacizumab, which is the standard-of-care in second line colorectal cancer.

We are hopeful that this randomized study will show a significant improvement in progression-free survival relative to the standard-of-care chemotherapy control arm. As we announced today, we have now treated the first patient in this randomized study. We also made great progress during 2022 in developing and understanding of the potential role of our T-cell engagers such as imvotamab in treating autoimmune diseases. We are encouraged by the expanded safety and efficacy data for imvotamab at a 100 milligrams that we have developed through our clinical studies in non-Hodgkin’s lymphoma, and we believe that imvotamab safety profile may be an important differentiating factor in the exciting new field of T-cell engagers in autoimmune disease. Building on our success in 2022, we expect that 2023 will also be an important year for the expansion and validation of IGM’s platform.

Already this year, we have treated the first patients in our clinical study of IGM-7354, an IgM targeted immunostimulatory IL-15 cytokine, which could be used for the treatment of patients with solid and hematologic malignancies. We are particularly excited about the potential to use IGM-7354 in combination with cellular therapies such as CAR-T and CAR-NK cells. We are also initiating studies of IGM-2644, our CD38 x CD3 bispecific IgM antibody, which we hope will be a safe and more potent form of anti-CD38 therapy for multiple myeloma, including for patients who have previously been treated with daratumumab. We also plan to file investigational new drug applications and initiate clinical studies for imvotamab in multiple autoimmune diseases this year, beginning with lupus and rheumatoid arthritis.

At this point, I’d like to turn the call over to Misbah to review our financial results for 2022.

Misbah Tahir: Thank you, Fred. In addition to the brief financial overview, I will provide on the call today, you can read additional detail on our fourth quarter and year-end financial results in our press release issued prior to this call and in our 10-K, which was filed with the SEC. We are fortunate to be in a strong financial position. In the second quarter of 2022, we received an upfront payment of $150 million from Sanofi related to our collaboration agreement and raised gross proceeds of $230 million in a follow on public equity offering. As a result, our cash and investments totaled $427.2 million as of December 31, 2022. In the fourth quarter, our research and development expenses were $45 million. For the full year 2022, R&D expenses were $179.3 million.

General and administrative expenses for the fourth quarter of 2022 were $11.6 million and $49.7 million for the full year 2022. Collaboration revenues for the fourth quarter of 2022 were $0.4 million and $1.1 million for the full year 2022. Our net loss for the fourth quarter of 2022 was $52.6 million or a loss of $1.19 per share. For the full year 2022, our net loss was $221.1 million or a loss of $5.32 per share. Turning now to the financial guidance for 2023. We expect our full year 2023 GAAP operating expenses to be between $290 million and $300 million. This includes estimated non-cash stock-based compensation expense of approximately $50 million. For the full year 2023, we also expect to recognize approximately $3 million of collaboration revenue related to last year’s upfront payment from Sanofi.

Finally, we expect to end 2023 with a balance of approximately $200 million in cash and investments providing IGM with an expected cash runway into the second half of 2024. With that, I’ll now turn the call over to Chris, our Chief Medical Officer.

Chris Takimoto: Thank you, Misbah. As Fred mentioned, 2022 was a very important year for the clinical development of IGM-8444. I am pleased to announce that we have now dosed more than 100 patients with IGM-8444 in our broad multi-indication, multi-combination Phase 1 study, and we’re very excited about the safety and clinical activity profile that we’ve seen to date in our combination with the standard FOLFIRI chemotherapy regimen in colorectal cancer patients. In January, we shared our initial data from our FOLFIRI combination cohort, which is available in detail in our current corporate overview presentation. To summarize, these data showed an encouraging safety profile that was broadly comparable to that expected from chemotherapy alone.

Specifically, no signs of drug related clinically significant hepatotoxicity were observed, as only Grade 1 and Grade 2 transient drug related liver enzyme elevations were seen. The substantial majority of our patients with metastatic colorectal cancer have been treated with 3 milligrams per kilogram of IGM-8444 in combination with FOLFIRI and thus far we have seen promising activity at that dose level with multiple confirmed responses even in patients who had previously progressed on prior FOLFIRI. We also saw encouraging progression-free survival in third and fourth line patients with one patient continuing for over a year without progression. These data have encouraged us to start treating patients with FOLFIRI plus bevacizumab, which is the current standard of care treatment for second line colorectal cancer.

I am pleased to announce today that we have now treated nearly 20 patients in combination with bevacizumab and we’ve not seen any additional toxicity signals arising from the addition of bevacizumab to the combination. These early safety and efficacy observations have encouraged us to proceed immediately into a randomized clinical study of FOLFIRI and bevacizumab plus or minus IGM-8444 in second line colorectal cancer. We are pleased to announce today that we have now dosed the first patient in this randomized clinical trial. We’re also excited to announce today that our analysis of the cell death biomarker caspase-3 in patients treated with IGM-8444 across multiple dose levels both as monotherapy and in combination showed a consistent increase post-treatment in 60 of 64 patients analyzed.

In addition, a dose-dependent increase was seen at the two highest dose levels tested of 3 and 10 milligrams per kilogram. A summary of these data is available in our current corporate overview slide deck available on our website. This biomarker signal has led us to add an additional 10 milligram per kilogram dose cohort to our randomized combination study. This protocol is currently being amended to randomized patients to three groups, either 3 or 10 milligrams per kilogram of IGM-8444 with FOLFIRI plus bevacizumab or standard of care chemotherapy alone. Our primary endpoint for this study will be progression-free survival with overall survival and response rate as secondary endpoints. We are exploring with the FDA potential randomized pathways to accelerated approval in accordance with their recently released guidance on this topic.

We also announced today that we are now treating patients in our fifth birinapant combination dose escalation cohort. To date, there have not been any observed dose limiting toxicities in combination with birinapant. We also announced today that we’ve treated the first patient in our IGM-8444 plus venetoclax and azacytidine combination in subjects with acute myeloid leukemia. Finally, we’ve also conducted extensive preclinical studies with other chemotherapeutic agents in combination with IGM-8444 in a variety of different cancer types. We plan to clinically evaluate one or more of these chemotherapy combinations with IGM-8444 as our development program expands. At this point, I’d like to turn the call over to Mary Beth Harler, our President of Autoimmunity and Inflammation.

Mary Beth will be leading our clinical development efforts for imvotamab in autoimmune diseases and as the clinical development in autoimmune diseases will be our focus going forward, she will be sharing today’s interim clinical updates about the imvotamab NHL program. Mary Beth?

Mary Beth Harler: Thank you, Chris. As you mentioned, we are announcing some encouraging safety and clinical activity data for imvotamab, which we think could offer a compelling and differentiated profile in the exciting new area of T-cell engagers in autoimmune disease. We think there is an important opportunity to bring forward a readily accessible therapy that offers deeper B-cell depletion than achievable with currently available anti-CD20 therapies. Also, you may recall hearing about some recent very encouraging data using CAR-T cells for B-cell depletion in lupus. We believe that imvotamab may have clear advantages over CAR-T therapies in autoimmune disease in terms of safety, cost and logistics. We announced today that as of our most recent data assessment, the incident of cytokine release syndrome was 9% overall safety evaluable patients treated with the 100 milligram titration dosing regimen in our Phase 1 and Phase 2 non-Hodgkin’s lymphoma studies, and it was 13% overall safety evaluable patients treated with either 100 milligrams or 300 milligram titration dosing in these Phase 1 and Phase 2 lymphoma studies.

All cases of CRS seen in the 100 milligram and 300 milligram titration dose cohorts were Grade 1 other than one Grade 2. We also announced today, although, the patient numbers are very small and additional patients currently on treatment may respond. As of the most recent data assessment, imvotamab has achieved a combined complete response rate of greater than 30% overall efficacy evaluable diffuse large B cell lymphoma or DLBCL patients in our Phase 1 and Phase 2 studies treated with the 100 milligram titration weekly dosing regimen, although, the patient numbers are too small to make a statistical assessment. Currently, the response rate in DLBCL continues to be appears €“ continues to appear to be lower at the 300 milligram dose. As you may recall, we have previously announced that we have seen complete responses with imvotamab in all four major NHL subtypes, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.

While it is not possible to directly extrapolate these encouraging efficacy data in NHL to what we might observe in autoimmune disease, it’s worth noting a couple of points. First, CD20 is a well-established target in multiple autoimmune diseases. And secondly, the imvotamab data in NHL clearly demonstrate that imvotamab effectively depletes B cells even rapidly growing lymphoma cells. In combination with these strong signs of clinical activity, we believe that imvotamab safety profile will be an important differentiating factor in the treatment of autoimmune diseases with T-cell engagers together with the potential to more effectively deplete pathogenic B-cell deep within tissues that may be refractory to current therapies. We believe there are significant unmet medical needs and commercial opportunities that imvotamab may address across a range of autoimmune diseases.

We have also announced today that we plan to file IND applications in the second quarter to begin clinical testing of imvotamab in both, severe systemic lupus erythematosus or SLE and in severe rheumatoid arthritis or RA. We are also evaluating a variety of additional autoimmune diseases for a potential third IND application later this year. With that I’ll turn the call back over to Fred.

Fred Schwarzer: Thank you, Mary Beth. We are pleased with the safety in clinical activity profile that we have seen with imvotamab at 100 milligrams in our non-Hodgkin’s lymphoma clinical studies to date, and we are excited to move forward aggressively in developing imvotamab for multiple autoimmune diseases. Given the relative size of the potential autoimmune markets and imvotamab’s potential competitive advantage in autoimmune disease resulting from its safety profile, we believe that the unmet medical needs and the commercial opportunities for imvotamab in autoimmune diseases are substantially greater than those in non-Hodgkin’s lymphoma, particularly those as monotherapy and relatively late lines of lymphoma treatment. As a result, we are announcing today that we are redirecting our clinical development efforts for imvotamab to autoimmune diseases and that we have decided to cease further monotherapy clinical development efforts for imvotamab in non-Hodgkin’s lymphoma.

We continue to believe that the safety and efficacy profile of imvotamab could position it well as a combination partner for the treatment of non-Hodgkin’s lymphoma, and we will be focusing our future efforts in NHL on evaluating combination opportunities and partnerships for imvotamab. With that I’d like to turn the call back to Chris to discuss our exciting early stage clinical development efforts in oncology.

Chris Takimoto: Thank you, Fred. As we announced in January we’re excited to have initiated a clinical trial exploring the safety, efficacy in pharmacodynamic activity of IGM-7354 and IgM targeted immunostimulatory IL-15 cytokine in the treatment of patients with solid tumors. We are announcing today that we’ve successfully dosed our first two patients with no drug related safety issues. We believe that IGM-7354 has the potential to be used in combination with a broad range of other drugs which rely on CD8 positive cells or NK cells for their activity, including combinations with CAR-T and CAR-NK cells. We are also announcing that the FDA has cleared our IND application for IGM-2644, a CD38 x CD3 IgM T-cell engager, which allows us to commence a Phase 1 dose escalation trial in patients with recurrent or refractory multiple myeloma.

This study will allow us to investigate the initial safety and efficacy of our next T-cell engaging IgM molecule. Our ultimate clinical development goal for IGM-2644 is to establish it as a safe and more potent anti-CD38 therapy, even for patients who have received prior daratumumab treatment. We are very excited by the potential for IGM-2644 to provide the next generation form of an anti-CD8 therapy. As you may recall in December of last year, we presented preclinical data at the 2022 ASH meeting showing that IGM-2644 achieved potent T-cell directed cellular cytotoxicity in multiple myeloma patient samples and in daratumumab resistance cell lines with minimal cytokine release. With that I’d like to turn the call back over to Fred.

Fred Schwarzer: Thank you, Chris. In closing, I’d like to thank all of the employees of IgM for their work over the past year. All of our principal investigators, their teams and their institutions and most importantly the patients and their families, all of whom have made the progress we’ve described today possible. We’re very excited about the progress that we hope to make in 2023 towards our goal of bringing new and important treatments to patients. We appreciate your interest in IgM and we look forward to keeping you all informed as to our progress. With that operator, I’d like to open the call for questions.

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Q&A Session

Operator: Thank you. And our first question is from Stephen Willey with Stifel. Your line is open.

Stephen Willey: Yes. Good afternoon, guys. Thanks for taking the questions. I guess a lot going on here. So the decision to add the 10 mg/kg dose to the randomized Phase 2. Can you maybe just €“ can you answer the question, I guess as to whether or not you’ve conducted any dose expansion with the 10 mg/kg dose in combination with Bev/FOLFIRI before you’re enjoying it into the randomized Phase 2. And then just any updated thoughts on when we might get a look at the remaining dose expansion patients, I guess those treated at the 3 mg/kg dose and any that you may have treated at the 10 mg/kg dose? And then I have…

Fred Schwarzer: Chris, would you like to take that one?

Chris Takimoto: Sure. Yes. Steve, thank you for the question. So the really the experience that we have with 8444 at 10 milligrams per kilogram, as you’re aware we explored a number of patients during the monotherapy dose escalation, and then when we started to combine with FOLFIRI. We did the expansion at 3 milligrams per kilogram, although we did treat three patients at 10 milligrams per kilogram with FOLFIRI. But it was really the biomarker data that we’re sharing with you now that really showed this increase in plasma caspase-3 levels that continued to increase as we went from 3 to 10 milligrams per kilogram, and that was one of the major factors that led us to incorporate and make the decision to add 10 milligrams per kilogram to the randomized study.

Plus we did get additional feedback from the FDA that was again very supportive of doing formal dose exploration and optimization in the study. So those were the things, the new biomarker data and that really prompted us to make this addition to the study.

Stephen Willey: Okay. And then I guess as a follow-up. Does the addition of the third arm to the randomized Phase 2 change your powering assumptions? And I know that you’re kind of guiding to potentially having a conversation with FDA regarding an accelerated approval pathway. So should we think about patient enrollment then as kind of a moving €“ a moving target?

Fred Schwarzer: Yes. So this study is built with a certain degree of flexibility, and again the study is really designed to confirm the signal that we have seen in our single arm experience in combining 8444 with FOLFIRI. But it’s also written so that when we can actually evaluate the impact of dose as well as looking at the primary endpoint, which is going to be progression free survival. And so we’ve left things somewhat open in terms of if we get a strong signal that allows us to pick a dose and also confirm the magnitude of the benefit over the control arm, there’s the potential that we can either stop this early and initiate a more formal registrational trial, or alternatively we could potentially with regulatory feedback expand this study to increase the number of patients on each of the arms and potentially use this as a randomized accelerated approval trial. So those possibilities are all things that we are considering as we move forward.

Stephen Willey: Okay. And then maybe just lastly, real quickly I know obviously imvotamab is getting prioritized for AI disease, but maybe for Mary Beth, can you just kind of speak to, I guess your interest in potentially looking at IGM-2644 in autoimmune disease as well? Thank you.

Mary Beth Harler: Yes. No, absolutely. Thanks Steve. As we are thinking about our T-cell engager assets morph through a portfolio lens than individual opportunities, and we are very excited about how these assets may come together to afford multiple therapeutic approaches to treating B-cell and plasma cell mediated diseases. As we discussed obviously CD20, a well-established target in autoimmune disease, CD38 some €“ there is a smaller, but very interesting data set particularly in the setting of diseases such as lupus to support the potential utility of CD38 targeting therapies. I think it is very important that we understand what the safety of our own CD38 x CD3 molecule looks like in multiple myeloma as we’ve discussed.