On November 3, 2022 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing IgM antibodies, reported its financial results for the third quarter ended September 30, 2022 and provided an update on recent developments (Press release, IGM Biosciences, NOV 3, 2022, View Source [SID1234622925]).

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"We have made substantial progress in advancing our IgM platform in the third quarter, particularly in expanding the body of evidence underlying our T cell engager portfolio for hematologic malignancies and in generating additional clinical data for IGM-8444. We continue to believe that each of our T cell engager product candidates has the potential to change the treatment paradigm in its respective indication. Notably, we are excited to share the first insight into the preclinical profiles of IGM-2644, our CD38 x CD3 bispecific IgM antibody, and IGM-2537, our CD123 x CD3 bispecific IgM antibody, during poster presentations at the upcoming ASH (Free ASH Whitepaper) meeting in December," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "Additionally, today we are providing an update from the Phase 1 dose escalation trial of imvotamab in relapsed and/or refractory NHL describing its durable benefit for relapsed and/or refractory NHL patients. We look forward to sharing an initial Phase 2 efficacy and safety update for imvotamab and an initial efficacy and safety update on the FOLFIRI combination for IGM-8444 in Q1 2023."

Pipeline Updates

Imvotamab (CD20 x CD3)

Biomarker data from the Phase 1 trial evaluating imvotamab, the Company’s novel IgM T cell engaging bispecific antibody, selected for presentation at 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held virtually and in-person in New Orleans, Louisiana, December 10-13, 2022. The results will be presented on Sunday, December 11, 2022, at 6:00 p.m. CT, in a poster presentation titled "Pharmacodynamics and Biomarker Correlates of Imvotamab (IGM-2323), the First-in-Class CD20 x CD3 Bispecific IgM Antibody with Dual Mechanisms of Action, in Patients with Advanced B Cell Malignancies."
Biomarker data obtained from patients in dose escalation cohorts will be presented illuminating the relationship between T cell levels and response as well as pharmacodynamic data confirming T cell dependent (TDCC) and complement dependent (CDC) mechanisms of action for imvotamab in patients. Biomarker data (minimal residual disease data) to support durability of response will also be presented.
The ASH (Free ASH Whitepaper) abstract is available through the ASH (Free ASH Whitepaper) online meeting program.

Clinical development of imvotamab advances. IGM today provided an update on response duration from the Phase 1 dose escalation study of imvotamab in patients with relapsed and/or refractory (R/R) non-Hodgkin’s lymphoma (NHL).
In data previously reported at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, imvotamab showed a 50% complete response (CR) rate at the likely optimal 100 mg dose (n=10). Of the 28 patients treated in the titration dosing cohorts at that time, cytokine release syndrome was seen in less than 20% of patients.
Seven of eight complete response patients were tumor free after more than 1 year as of the data cut-off of August 31, 2022, and as of the data cut-off, the median overall duration of response in these patients had not yet been reached. All DLBCL patients with a complete response reported as of ASH (Free ASH Whitepaper) 2021 remained in complete response. Seven responding patients switched from weekly to Q3W therapy and all remain on study with sustained responses.

IGM expects to provide an initial Phase 2 efficacy and safety update for imvotamab in the first quarter of 2023.

Announced clinical trial collaboration and supply agreement with ADC Therapeutics SA. IGM expects to initiate clinical testing evaluating the combination of imvotamab and ZYNLONTA (loncastuximab tesirine-lpyl), ADC Therapeutics’ CD19-directed antibody drug conjugate (ADC), for the treatment of patients with R/R NHL in the first quarter of 2023.
IGM-2644 (CD38 x CD3)

Preclinical data for IGM-2644, the Company’s CD38 x CD3 bispecific IgM antibody, selected for poster presentation at 2022 ASH (Free ASH Whitepaper) Annual Meeting and Exposition. The results will be presented on Sunday, December 11, 2022, at 6:00 p.m. CT, in a poster presentation titled "IGM-2644, a Novel CD38 x CD3 Bispecific IgM T Cell Engager Demonstrates Potent Efficacy on Myeloma Cells with an Improved Preclinical Safety Profile."
Preclinical data will be presented that highlights the potency of IGM-2644 with potential activity in daratumumab resistant tumors and a preclinical safety profile with lower cytokine release and reduced T cell fratricide compared to other CD38 x CD3 bispecific T cell engagers.
The ASH (Free ASH Whitepaper) abstract is available through the ASH (Free ASH Whitepaper) online meeting program.

Phase 1 trial expected to initiate in first quarter of 2023. IGM expects to initiate a Phase 1 trial of IGM-2644 in multiple myeloma in the first quarter of 2023, subject to IND clearance.
IGM-2537 (CD123 x CD3)

Preclinical data for IGM-2537, the Company’s CD123 x CD3 bispecific IgM antibody, selected for poster presentation at 2022 ASH (Free ASH Whitepaper) Annual Meeting and Exposition. The results will be presented on Sunday, December 11, 2022, at 6:00 p.m. CT, in a poster presentation titled "CD123 Directed IgM Antibody-based T-cell Engager, IGM-2537, Demonstrates Potent in vitro and in vivo Activity with Minimal Cytokine Release."
Preclinical data will be presented highlighting potent in vitro and in vivo activity with minimal cytokine induction providing initial evidence of a favorable preclinical safety profile for a CD123 directed IgM-based T cell engager.
The ASH (Free ASH Whitepaper) abstract is available through the ASH (Free ASH Whitepaper) online meeting program.

IND application expected to be filed next year. IGM expects to file an IND application for IGM-2537 in acute myeloid leukemia in 2023.
IGM-8444 (DR5)

Clinical development of IGM-8444 advances. IGM continues to advance the clinical development of IGM-8444, the Company’s IgM DR5 agonist, in an open-label, multicenter, Phase 1 clinical trial in multiple combination treatment regimens in subjects with relapsed and/or refractory solid and hematologic cancers.
Expansion dosing ongoing in the FOLFIRI combination. IGM continues to enroll patients in an expansion of its 3 mg/kg FOLFIRI combination dose cohort in colorectal cancer patients, and it has recently further expanded this 3 mg/kg dose cohort to include treatment with IGM-8444 in combination with both bevacizumab and FOLFIRI in colorectal cancer patients. After completion of these 3mg/kg expansion cohorts, IGM expects to begin expansion of its 10 mg/kg FOLFIRI combination dose cohort. The Company expects to provide an initial efficacy and safety update on colorectal cancer patients treated with 3 mg/kg of IGM-8444 plus FOLFIRI in the first quarter of 2023.
Dosing ongoing in the fourth birinapant dose cohort. IGM is currently enrolling patients in the fourth planned birinapant combination dose escalation cohort.
IGM-7354 (IL-15 x PD-L1)

Phase 1 trial to initiate in the first quarter of 2023. IGM reported that it expects to dose the first patient in the Phase 1 trial for IGM-7354, IGM’s targeted IL-15 IgM antibody for the treatment of patients with solid and hematologic malignancies, in the first quarter of 2023, subject to IND clearance.

Preclinical data to be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. The poster, titled "IGM-7354, an anti-PD-L1/IL-15 IgM immunocytokine, activates and expands NK cells and effector memory CD8+ T cells in vivo" will be made available beginning at 9:00 a.m. ET on Thursday, November 10, 2022, through the SITC (Free SITC Whitepaper) online meeting program.
Corporate Updates

Albert Candia, Ph.D., appointed Senior Vice President of Preclinical Sciences. Dr. Candia brings over 22 years of biotechnology experience to IGM in both research and development in a variety of therapeutic areas and drug modalities. Prior to joining IGM, he was Vice President of Bioanalytical Development at Nektar Therapeutics, leading cross functional teams supporting clinical development and chemistry, manufacturing and control. Dr. Candia has also held previous positions at Dynavax Technologies and Xencor, where he oversaw IND enabling, translational and biomarker activities. Dr. Candia received his B.A. in Biology and Chemistry from Bucknell University and a Ph.D. in Cell Biology from Vanderbilt University School of Medicine.
Third Quarter 2022 Financial Results

Cash and Investments: Cash and investments as of September 30, 2022 were $469.1 million, compared to $229.5 million as of December 31, 2021.
Collaboration Revenue: For the third quarter of 2022, collaboration revenue was $0.3 million, compared to no revenue for the same period in 2021.
Research and Development (R&D) Expenses: For the third quarter of 2022, R&D expenses were $48.2 million, compared to $34.2 million for the same period in 2021.
General and Administrative (G&A) Expenses: For the third quarter of 2022, G&A expenses were $12.7 million, compared to $10.0 million for the same period in 2021.
Net Loss: For the third quarter of 2022, net loss was $58.0 million, or a loss of $1.32 per share, compared to a net loss of $44.2 million, or a loss of $1.32 per share, for the same period in 2021.
2022 Financial Guidance
IGM is updating its financial guidance and expects to end 2022 with a balance of more than $410 million in cash and investments and full year GAAP operating expenses of $240 million to $245 million including estimated non-cash stock-based compensation expense of approximately $45 million. IGM estimates full year collaboration revenue of approximately $1 million related to the Sanofi agreement.