ImmunoGen: What About Now?

ImmunoGen is one of two firms Prohost selected for investment on February 2011 based on the promises of its novel antibody-drug conjugate (ADC). An ADC drug is an antibody that carries highly potent cancer-killing agent attached to the antibody by a linker. The linker is designed to release an exceptionally toxic agent only as the ADC reaches the cancer cells in order not to harm or kill healthy cells. Our enthusiasm for ADC products emanates from their potency compared to other antibodies and to their safety and potency compared to chemotherapy drugs. The dosage of the toxic agent in the monoclonal antibody conjugate is several times that of chemotherapy, hence the superior potency and tolerability expected from the ADC products.


ImmunoGen’s value cannot yet be found right now in its financial quarterly results. The reason is that the real value of ImmunoGen is still in its pipeline ADC products and in their promises as demonstrated in study results. The promises of ADC products are what led us to bet on IMGN in the first place as no criteria of evaluation matter for a development-stage firm except the promise of the investigational pipeline products. Immunogen’s pipeline is notably rich, comprising eighteen ADC products, with sixteen in various Phases of clinical trials and two ADC advanced products in preclinical studies.

Of the sixteen ADC products in clinical trials, three have reached Phase 3 trial; four are in Phase 2 and nine in Phase 1 trials. Thirteen of all eighteen products are licensed to collaborators in return for upfront, milestone and royalty payments and five ADC products belong to ImmunoGen, including the lead investigational product Mirvetuximab soravtansine, which is in pivotal Phase 3 trial for ovarian cancer, and in a multitude of trial for various cancers.


As we explained above, ImmunoGen licensed 13 products to pharmaceutical companies and kept five products for itself. The lead investigational ADC product Mirvetuximab soravtansine (IMGN853) is the lead product in the wholly-owned ImmuoGen’s pipeline of ADC products  

1. Mirvetuximab soravtansine is a potential new treatment for patients with folate receptor alpha (FRα)-positive cancer, including many with ovarian cancers and others with other folate receptor alpha (FRα)-positive solid cancers. The product is in Phase 3FORWARD I clinical trial as a single agent for the treatment of platinum-resistant ovarian cancer. It is also being also being assessed in combination regimens for both platinum-resistant and platinum-sensitive disease in the Phase 1b/2 FORWARD II trial. It is also in clinical study as a single-agent therapy for patients with FRα-positive ovarian cancer treated with 3-4 prior regimens.

FORWARD I is a Phase 3 trial in which 333 patients are randomized 2:1 to receive either mirvetuximab soravtansine or the physician’s choice of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel). Eligible patients will have been diagnosed with platinum-resistant ovarian cancer that expresses medium or high levels of FRα and will have been treated with up to three prior regimens. The primary endpoint of this study is progression free survival (PFS). 

In FORWARD I clinical trial, ImmunoGen is partnering with the GOG Foundation, which is a clinical research gynecologic malignancies Foundation.

The drug is being tested on other difficult-to-treat cancers, including triple negative breast cancer and other solid and hematology cancers. 

Immunotherapy Combination: Mirvetuximab soravtansine is being tested in combination regimens with Merck’s immune checkpoint inhibitor KEYTRUDA (pembrolizumab) and with other existing drugs belonging to other pharmaceutical companies.

FEEDBACK: Investigators of Mirvetuximab Soravtansine concluded that the product demonstrated safety and activity in platinum-resistant ovarian cancer.

The strongest signals of efficacy: Observed in the less heavily pretreated individuals.

The dose, schedule, and target population: All have been identified for a phase 3 trial of IMGN853 monotherapy in patients with platinum-resistant ovarian cancer.

Kathleen Moore, M.D., the Co-Principal Investigator of FORWARD I trial, and Associate Professor, Stephenson Cancer Center, University of Oklahoma remarked, “Given the prognosis for most patients with platinum-resistant ovarian cancer is poor and the benefit of approved agents is modest, we need better therapies that offer improved outcomes in terms of efficacy and tolerability. We are excited about the potential of mirvetuximab soravtansine and are looking forward to evaluating this promising agent in the pivotal study.

Important to note that FORWARD I trial is intended to support full marketing approval of mirvetuximab soravtansine for patients with platinum-resistant ovarian cancer.

2. IMGN529: This ADC drug targets CD37. It is in Phase 1b/2 clinical trials for B-cell malignancies, which include non-Hodgkin lymphoma (NHL).

Feedback: The drug demonstrated initial evidence of anticancer activity in NHL in early clinical testing designed to establish its dose. IMGN529 has demonstrated synergy when given with rituximab. A combination of IMGN529 plus rituximab is in Phase 2 trial.

3. Coltuximab Ravtansine: This ADC product targets CD19 for the treatment of diffuse large B-cell lymphoma (DLBCL). The product is in Phase 2 clinical trial for B-cell malignancies.

Feedback: in the STARLYTE Phase 2 clinical trial, Coltuximab Ravtansine conjugated monoclonal antibody demonstrated evidence of anticancer activity in relapsed/refractory DLBCL

4. IMGN779: This ADC product is the first ADC to utilize one of ImmunoGen’s new family of indolino-benzodiazepine cancer-killing agents. The new linker is designed to be ultra-potent, yet provide the tolerability necessary for ongoing retreatment. That’s what makes this ADC product top potent first-in-class ADC drug. IMGN779 is for cancers expressing CD33, including acute myeloid leukemia (AML.) The ADC product is designed to selectively target cancer cells that express CD33 and kill them via the improved payload agent DGN462.

5. IMGN632: An antibody drug conjugate targeting CD123 for the treatment of hematological malignant tumors, including AML. The product is for AML; formyelodysplastic syndrome; and B-cell acute lymphocytic leukemia, in addition to other CD123-positive cancers. To create this product, ImmunoGen attached a novel payload, linker and a new antibody technology. In other words, the new preclinical drug is an improved ADC drug.

Feedback: In preclinical models, the improved IMGN 632 has demonstrated an impressivetherapeutic window against CD123-positive malignancies. The product demonstrated potent in vitro and in vivo activity against AML cell lines and AML patient samples, including those with poor prognostic markers. The product was found to be active against AML cells with FLT-3 mutations and with the P53 mutation with established multidrug resistance.

Prohost Observations

The current ImmunoGen, we believe, must be embraced and encouraged rather than undervalued and destroyed. The past damages that harmed ImmunoGen’s finances, its standing and market value did not diminish the values of its great science, inspired scientists and impressive potent ADC cancer products’ results.

ImmunoGen’s ADC products, we believe, are valuable and badly needed to reach the market so that they can fill a void, which still exists in the new carefully structured pipeline with the ambitious goal of declaring definitive victory on the ongoing war on cancer.

Since we picked IMGN and SGEN, Prohost never abandoned these two ships, which have similar technologies that led l to the creation of the ADC potent products. We never abandoned SGEN after it rallied from $14 to $68.26 as we believe its pipeline products can generate revenues that exceed by far its current market cap. We never walked away from IMGN either when it plunged from $8.50, the day we picked it to less than $1.70 and then further bottom. We considered IMGN’s bottoming an opportunity to further accumulate the stock that has ultimately rebounded to reach $.4.44 as per yesterday’s closing price.

The core for our reasoning was the value of the firms’ technology and cancer products. We believed the ADC products are valuable. We believed they will have a big role to play in the management of cancer. This notion was reinforced following the emergence of the new immunotherapy breakthrough approaches for cancer treatment such as the checkpoint inhibitors and the CAR-T immunotherapy. It was obvious that these novel approaches were demonstrating better results when used in combination with other targeted products, which ImmunoGen’s and Seattle Genetics’ are saturated with.

The ADC technology and products have been validated through the approvals of drugs from both Immunogen and Settle Genetics and the presence of large number of pharmaceutical Companies that licensed both firms’ ADC technology, or partnered on its products.

The big event that might have encouraged a very large number of negative traders, investors, and institutions to short IMGN and cause a general stock selloff happened the next day the FDA approved ImmunoGen’s ADC drug Kadcyla for HER2 positive breast cancer. The product was developed by Genentech. During the conference call announcing the great news, the analysts, one by one, unveiled that the fact that the terms and percentage of the royalty payments as accepted by ImmunoGen were unacceptably poor and would not improve the finances of the struggling scientific genius firm.

This revelation left investors with the belief that ImmunoGen a firm that has more than half of its pipeline products being developed by other firms, probably holding collaborating agreements that were bad for it. They saw ImmunoGen having no cash to develop any of its promising products. The negative picture was a great gift handed to short analysts and investors who didn’t hesitate to make their big moves. They started by magnifying insignificant setbacks, exaggerating the impact of the firm’s obvious negative quarterly financial results, in addition to criticizing every decision the firm has been forced to make in order to prevent its evaporation with its evaporating cash and its dissolving value in Wall Street.

The only thing that still remained unharmed, though, was ImmunoGen pipeline of ADC products. This is what we bet on in the past and continue to do the same now.

A bottomed stock can take its firm in one of two different directions: Rallying in case the firm is really undervalued, or bankrupting in case nothing remained valuable in the firm. ImmunoGen had its valuable pipeline of ADC products intact and regenerated, and its collaborators continuing to work hard on many of its ADC products. It was clear that its stock direction will be staging a rally rather than fading away. It was also clear that the rally will lead to a short squeeze.  It did.

What about now?

We will obviously continue what we are doing, i.e., stay on board and wait for the approaching catalysts, which start with the results of Mirvetuximab soravtansine on ovarian cancer. We will also wait for the results of ImmunoGen’s drugs’ combinations with immunotherapy drugs and with other targeted and non-targeted drugs.

This time there is no fear from bad agreements. The lead product is wholly-owned by Immunogen and so are its four other ADC products.

For those who might have other strategies, including taking their profits now and tomorrow is another day, we have nothing to say against this strategy. But in this case we would rather prefer to take the middle way, i.e., sell some and keep some so we can satisfy today without ignoring tomorrow.

Prohost Forward-Looking: Material presented here is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock you should do your own research and reach your own conclusion. Further, these are our ‘opinions’ and we may be wrong. We may have positions in securities mentioned in this article. You should take this into consideration before acting on any advice given in this article. If this makes you uncomfortable, then do not listen to our thoughts and opinions. The contents of this article do not take into consideration your individual investment objectives so consult with your own financial adviser before making an investment decision. Investing includes certain risks including loss of principal.

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