Immunogen (IMGN) is a mid-cap company that focuses on the development of Antibody-Drug Conjugates (ADC) for the treatment of various cancers. Their lead internal candidate has of late been mirvetuximab soravtansine for the treatment of ovarian cancers. Investor may remember that Immunogen’s prior phase three trial FORWARD I failed to meet its primary endpoint. While this informed the company and investigators on how to design additional registrational trials, it delayed Immunogen’s transition from a clinical stage company to a commercial stage company. As it stands today, Immunogen is still pursuing and developing mirvetuximab soravtansine for ovarian cancer.
Current Status of Mirvetuximab Soravtansine in Ovarian Cancer
Mirvetuximab soravtansine targets the Folte receptor alpha (FR-A), carrying a toxic payload to the cells that express this receptor. This receptor can be expressed in varying degrees, and thus after the failure of FORWARD I, Immunogen has two trials designed to bring mirvetuximab soravtansine to patients with high expression of FR-A , platinum-resistance ovarian cancer. This will be done through two trials, the first being SORAYA which could lead to accelerated approval, and then MIRASOL which would serve as the confirmatory clinical trial leading to full approval in the indication of FR-A high, platinum resistant ovarian cancer. The expected timelines for data and approvals for these two trials are presented in Figure 1.
As noted above, there are additional indications in ovarian cancer for which Immunogen is pursuing development. These indications are for earlier lines of therapy in combination with other agents such as bevacizumab and carboplatin, which are backbone therapies for ovarian cancer. Immunogen has shared that they are still evaluating the most effective way to expand the potential regulatory approvals for mirvetuximab soravtansine in these earlier lines. Additionally, Immunogen has a second FR-A ADC in preclinical development, which is called IMGN151. This new agent has made several improvements on mirvetuximab soravtansine which may prove efficacious in patients with medium or low expression of FR-A. The preclinical data presentation is available here.
IMGN632 for BPDCN
IMGN632 is an antibody drug conjugate that targets the protein CD123 on the surface of certain cancer cells. Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and aggressive blood cancer that has limited therapeutic options, and as such, has poor survival outcomes. When we say rare, this means that there are roughly 1,000 to 1,400 cases annually in the US and Europe combined. SO that being said, this is not the largest market. What is notable, is that CD123 is over expressed in nearly all cases of BPDCN, which allows for a therapeutic target in drug development. In late 2018, the FDA approved the first, and still the only, drug to treat BPDCN. This drug was tagraxofusp (brand anme: Elzonris). This drug is similar to IMGN632 in that both drugs target CD123. However, while IMGN632 is an antibody drug conjugate, Elzonris is a protein that is composed of a fusion protein which results in cell death for this cells expressing CD123. Seeing as Elzonris is the first and only drug approved for BPDCN, it is highly likely that this drug will be the measuring stick for which IMGN632 will be compared to. So lets take a look at the data for Elzonris.
Elzonris was studied in 15 patients with relapsed or refractory BPDCN. Of these 15 patients, one patient achieved a complete response, and one patient acheived a complete clinical response. If we combine these two respones, we get an overall response rate of 13%. Turning to durability, the patient achieving a complete response had a duration of 111 days, while the complete clinical response lasted 424 days. Now that we have touched up efficacy, let’s look at safety. Elzonris has a black box warning for capillary leak syndrome (CRS) which can be a fatal if not managed properly. In fact, this was fatal in around 2% of patients receiving Elzonris in clinical trials. Furthermore, almost 50% of patients receiving Elzonris experienced allergic reactions to the drug. Finally, Elzonris has been associated with liver toxicity, with elevated liver enzymes being seen in 88% of patients on treatment. Finally, the dosing of Elzonris is an IV infusion over 15 minutes once daily for 5 days straight every 21 days.
https://www.immunogen.com/wp-content/uploads/2020/12/IMGN632_ASH2020_801-Oral-Presentation-Slides-Only_vF-1.pdfThe data that Immunogen presented at ASH focused on the treatment of relapsed and refractory BPDCN in 29 patients. Starting on the safety standpoint, IMGN632 appears to be far better tolerated than Elzonris. In the patients presented, there were no instances of capillary leak syndrome, no patients discontinued the drug due to side effects, and there were no deaths related to the administration of the drug. Finally, there were very minimal evidence of liver toxicity. All in all, the data presented for IMGN632 clearly favor a safer drug than Elzonris.
Moving on to efficacy, the overall response rate was 29%, which did include an 18% composite clinical response rate. This undoubtedly exceeds the efficacy bar of Elzonris. Furthermore, and even more encouragingly, was that the overall response rate of IMGN632 was 31% in patients who had previously received Elzonris. This is particularly important as it suggest that receipt of one CD123 targeted agent does not preclude a patient to be treated with IMGN632, also a CD123 targeting agent. Another benefit of IMGN632 over Elzonris is the dosing regimen. While Elzonris requires 5 daily infusions every 21 days, IMGN632 requires only 1 infusion every 21 days, which provides convenience for patients.
In summary, I find this data extremely promising and encouraging. I see no reason why IMGN632 should not be the preferred therapeutic agent in relapsed and refractory BPDCN. Since Immunogen’s development of this drug is ongoing, we will see if the positive comparisons to Elzonris continue in the front line setting. I would speculate that IMGN632 will retain it’s clear differentiation with regards to safety and patient convenience. The question then becomes how will its efficacy compare? Hopefully these questions will be answered soon. It is notable the the FDA has granted Immunogen Breakthrough Therapy Designation for IGN632 in the treatment of BPDCN. What does this mean? Well Breakthrough Therapy designation is designed to expedite the development and review of drugs that are intended to treat a serious condition and have generated preliminary clinical evidence that the drug may demonstrate substantial improvement over available therapy. What is most notable for investors, is that this designation can help facilitate accelerated approval. Which in my opinion, means we could see an BLA filed for IMGN632 within the next 12 months based on the clinical data that has been generated thus far. In my opinion, the gating actions that could hold back this filing would be the non-clinical data such as manufacturing, stability, and sterility data. But in my opinion, IMGN632 has clearly generated enough clinical data to be perceived as a valuable and needed therapeutic option for BPDCN patients.
Immunogen Financials and Final Thoughts
At the close of trading on 12/4, Immunogen had a market cap of $1.13 billion. They ended the third quarter with $188.2 million in cash and cash equivalents. However, subsequent to the quarter ending, Immunogen bolstered the balance sheet with $54 million raised via their At-the-Market facility and received an upfront licensing payment of $40 million from Haudong Medicine. In the first 9 months of 2020, Immunogen utilized $87.2 million for operations, but with roughly $282 million (pro-forma) in the bank, we can see that cash runway is not a concern for Immunogen. As trials continue to enroll/expand, and regulatory activities pick up, I do anticipate that expenses will increase, however I am not concerned at this point.
All in all, Immunogen has generated a lot of positive momentum this year. They are positioned for an exciting next 1-2 years with ovarian cancer developments and BPDCN filings. It is reassuring that Immunogen has signed several out-licensing agreements that provide external validation of the platform. I beleive that what we see here is a young SeaGen (SGEN) or Immunomedics (IMMU) in the making which will provide a profitable payday for those investors who are patient.
I/we long IMGN.
This is in no form a recommendation to buy or seel securities.