IGM Biosciences, Inc. (NASDAQ:IGMS) has built a substantial pipeline full of a few clinical candidates that have been progressing in the clinic. One such drug would be imvotamab, which is a CD20 X CD3 bispecific T cell engaging antibody being developed for the treatment of patients with autoimmune disorders. It is already advancing two phase 1b studies using this drug to treat patients with severe systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) respectively. Why I believe that investors should keep an eye on this company is because it is expected that initial results from both of these phase 1b studies are going to be released in the 2nd half of 2024.
There is a third candidate which is also in clinical trial preparation as well, in that IGM Biosciences received clearance to initiate an early-stage study using imvotamab for the treatment of patients with idiopathic inflammatory myopathies (myositis). This provides another shot on goal for this drug, which could end up boosting shareholder value. Even if the use of imvotamab doesn’t work out, it does have another candidate in the pipeline it is working on. This would be with respect to the testing of DR5 receptor cross-linking agonist Aplitabart for the treatment of patients with 2nd-line metastatic colorectal cancer. This drug is being explored in two studies for the treatment of this patient population.
One study is a single-arm one whereby 10 mg/kg of Aplitabart combination is being given to these patients. The other study is a randomized one using 3 mg/kg of this drug together with FOLFIRI and bevacizumab (AVASTIN) to target them. The point is that enrollment for both the single-arm study and the randomized study, are expected to complete enrollment in the 1st half of 2024 and Q1 of 2024, respectively. The data should be released from them by the 2nd half of 2024. With several catalysts on the way using two different clinical candidates, plus the advancement of next generation candidates, I believe that investors could benefit from any gains made.
Imvotamab Moving Forward With Two Early-Stage Programs Against Autoimmune Disorders
As I explained above, IGM Biosciences is advancing the use of Imvotamab for the treatment of patients with autoimmune disorders. It is actively enrolling for two early-stage phase 1b studies using this drug to treat patients with severe systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). The first phase 1b study is using this drug to target patients with SLE, but one main thing to note is that it is only being done as an open-label, single-arm study. That means there is no placebo comparator for these severely sick SLE patients. It is expected that a total of 18 patients will be recruited into this one.
The second phase 1b study is using this drug to treat patients with RA. However, this will actually be a double-blind placebo-controlled study. It is expected that a total of 24 patients will be recruited into this one. Both of these early-stage trials are incorporating a sequential dose-escalation cohort design as follows:
- Cohort 1 : 5 mg -15 mg -30 mg – 100 mg.
- Cohort 2 :10 mg – 30 mg – 100 mg – 300 mg.
- Cohort 3 : 15 mg – 50 mg – 300 mg – 600 mg.
The purpose of this design is to escalate dosage to see what could be attainable in the end with respect to safety/efficacy data. Systemic Lupus erythematosus ((SLE)) is a type of disorder characterized as the immune system starting to attack the tissues and organs of a person. It is a chronic illness that targets many parts of the body such as: Skin, joints, kidneys, brain, blood cells, lungs and many others. The global lupus market size is projected to grow to $6.78 billion by 2032. Rheumatoid arthritis [RA] is characterized as a chronic inflammatory autoimmune disorder that has a major negative impact on a person’s joints. It primarily affects joint linings in the body, which can then be a major cause for painful swelling occurring. The global Rheumatoid Arthritis drugs market size is projected to reach $38.61 billion by 2032. This is another large target market indication that the biotech could go after.
The opportunity with respect to both of these markets is extremely ideal. That’s because investors won’t have to wait long to see if this next generation CD20 X CD3 bispecific T cell engager is capable of being able to have a major impact on treating patients with either SLE or RA. That’s because it is expected that results from each of these phase 1b studies could be released by the 2nd half of 2024.
Other Possible Targets Being Engaged Creating Expansion Opportunities
The premise of IGM Biosciences is to build upon initial science and expand upon it. What do I mean? well, IgG antibodies have been known to do well in treating cancer, autoimmune disorders and other inflammatory diseases. However, they only have two binding units, which means structurally that they can only link up to 2 binding sites on an antibody target. This means that there is not a great avidity occurrence that occurs.
What is “Avidity”? In essence, the ability to bind to multiple sites at once on an antibody. How imvotamab does this is by having an IgM structure, instead of an IgG one. This unique pentameric IgM structure allows for 10 binding sites, instead of only 2 seen with the IgG type. Thus, this creates greater binding across multiple points of the target or Avidity. Another improved item to note is that IgM antibodies have greater affinity [binding strength]. Not only that, but such affinity can be adjusted depending upon what is needed to target a specific type of disease. The last way to note on why this company is ideal compared to many other competitors, would be its J-chain design, which allows the use of bi-specifics (CD20 X CD3). All of these additional features may not only provide a competitive advantage over other antibody-based candidates in development, but may provide for greater B-cell Depletion across the entire spectrum. That is, efficacy can be improved upon compared to other B-cell depleting clinical candidates in development or approved.
There are two expansion opportunities that exist here. The first of which is the use of CD20 X CD3 bispecific T cell-engaging antibody imvotamab for the treatment of patients with idiopathic inflammatory myositis. That’s because IGM Biosciences received IND clearance to begin early-stage phase 1 testing for this target indication using this drug candidate.
A second expansion opportunity would be incorporating different bi-specifics depending upon what B-cell mediated autoimmune disorder is being targeted. For instance, there is a candidate in the pipeline known as IGM-2644 that is being developed to treat patients with autoimmune disorders. However, this T-cell engager incorporates bispecific CD38 X CD3 instead.
The main thing to note here is that this biotech can put in place any bispecific in place that it wants to target a broad range of B-cell expressions across the entire lineage. This flexibility means the ability to target a host of autoimmune disorders whereby other antibody-based therapies are limited in doing so. A catalyst opportunity for this candidate is also expected to take place this year. It is expected that IGM Biosciences will file an IND of IGM-2644, to begin phase 1 testing for the treatment of patients with autoimmune disorders, in 2024.
According to the 10-Q SEC Filing, IGM Biosciences had cash and investments of $387 million as of September 30th 2023. The thing is that this biotech made a deal with Sanofi (SNY) back in March of 2022. Such a deal was established in order to advance the IgM antibody technology to advance three agonist drugs against 3 oncology indications and then three immunology and/or inflammation targets. With respect to this deal, IGM Biosciences received a total of $150 million as an upfront payment and then has the potential to earn over $6 billion in aggregate development, regulatory and commercial milestones.
With the release of its earnings in the 10-Q SEC Filing, it believes that its cash of $387 million would be enough to fund its operations into the 2nd half of 2025. However, the company made a pipeline reprioritization, along with reducing its workforce. It chose to abandon its hematological pipeline with respect to its IgM antibody technology to focus on oncology/autoimmune disorders. Then, it reduced its workforce by 22% in order to conserve cash. Thus, establishing the new projection of ending December 31st 2023 with $338 million. These cost-cutting measures though are a good thing, because it now has enough cash to fund its operations well into Q2 of 2026.
Risks To Business
There are several risks to consider when investing in IGM Biosciences. The first risk to consider would be with respect to advancement of imvotamab for the treatment of patients with autoimmune disorders like severe systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Both of these are being explored in ongoing phase 1b studies with data readouts that could come towards the end of 2024. It is believed that the pentameric structure of enabling 10 binding sites using IgM imvotamab, over traditional IgG antibody-based approaches, will translate to superior avidity (binding/efficacy). There is no assurance that such avidity will be observed in these two studies, nor that positive data from either targeting SLE or RA will be released.
A second risk to consider would then be with respect to Aplitabart a cross-linking DR5 receptor agonist being developed for the treatment of patients with 2nd-line metastatic colorectal cancer (mCRC). As I explained above, IGM Biosciences is targeting this patient population in two different early-stage studies. One study is a single-arm one and then the other would be the randomized one, both of which are using Aplitabart alone and in combination with FOLFIRI and AVASTIN to treat these patients with this type of advanced cancer. It is not assured that positive results will be established for either one or both of these phase 1 studies for starters. Nor that the pentameric structure of being able to achieve cross-linking of DR5 receptors, will translate into increased apoptosis. DR5 receptors in the past had limited activity (terrible apoptosis capability) and poor safety for over 20 years. It is believed that the cross linking of DR5 receptors caused by Aplitabart could end up resulting in improved apoptosis [cell death] for this cancer. Best of all, is that this cross-linking technology with DR5 receptors not only can achieve improved efficacy, but does so with no cytotoxicity across a broad range of dosing. Such was observed in preclinical assays and if this translates to human data, then that will be highly ideal.
The third and final risk to consider would be with respect to the advancement of IGM-2644, which is a CD38 X CD3 being advanced for the treatment of patients with autoimmune disorders. As I briefly discussed above, the goal is to be able to generate greater avidity by being able to target 10 domains with the pentameric structure with IgM drugs, compared to two domains in IgG antibodies. The J-Chain in IgM allows for the company to place in whatever novel bispecific it so chooses.
In the case of IGM-2644, it has put in place the bispecifics of CD38 X CD3. Even if imvotamab using CD20 X CD3 is successful in treating patients with B-cell mediated autoimmune disorders in clinical studies, there is no assurance that avidity nor affinity [greater binding at specific domain sites] will be achieved. Thus, there is no assurance that positive data will eventually be released from a phase 1 study here.
IGM Biosciences, Inc. has done well to cut its costs and reprioritize its pipeline. This cost-cutting measure will allow to have enough cash to fund its operations until the 2nd half of 2026. Thus, the first good aspect to consider is that there is no risk of any near-term dilution that will occur.
The cash position alone is enough to consider this biotech, but this company has been able to establish clinical candidates with two different approaches. It is advancing a pentameric structure of DR5 with cross-linking agonism capability of Aplitabart treating patients with 2nd-line metastatic colorectal cancer. It is expected that the global colorectal cancer market is expected to reach $24.08 billion by 2028. Then, it is also using a pentameric structure drug for greater domain avidity/affinity targeting, known as imvotamab. Such a clinical candidate is being developed as a bispecific T-cell engager for the treatment of patients with various types of autoimmune disorders.
It is believed that the targeting of 10 binding domain units for patients with severe SLE or RA, could lead to improved clinical outcomes. This remains to be seen, but it is another shot-on goal for investors to consider here. The hope is that the IgM antibody-based technology approach by this biotech allows for patients to ultimately achieve improved B-cell depletion of their respective disorders.
Editor’s Note: This article discusses one or more securities that do not trade on a major U.S. exchange. Please be aware of the risks associated with these stocks.