Immunogen (NASDAQ:IMGN) is a nanocap clinical stage biopharma developing Mirventuximab soravtansine, an antibody-drug conjugate (NYSE:ADC) with a monoclonal antibody (mirventuximab) that binds to FRalpha-positive tumor cells thereby delivering its cytotoxic payload, soravtansine or DM4. The drug candidate is being examined in combo with Keytruda for ovarian cancer under an agreement with a Merck subsidiary. The company was recently under the scanner for cutting its work force, making a secondary offering, and a few critical management changes. On the basis of positive phase 1 data, the company has initiated a phase III study, FORWARD I to evaluate mirvetuximab soravtansine as single-agent therapy in patients with platinum-resistant ovarian cancer who previously received up to three treatment regimens and whose cancer has a medium or high FRα expression. It is also being evaluated with other regimens in phase Ib/II FORWARD II study for the treatment of both platinum-resistant and platinum-sensitive disease. Some data is expected by mid-2017.
Immunogen's ADC technology has been used by a number of partners, notably by Roche to develop its blockbuster drug Kadcyla, which consists of IMGN's "DM1 cell-killing agent attached to Roche's HER2-targeting antibody, trastuzumab, using our SMCC linker ("emtansine" is DM1 attached using SMCC)." Its entire pipeline looks like this:
Mirvetuximab Soravtansine is its only wholly-owned drug candidate in phase 3. In this article, we will focus on Mirvetuximab Soravtansine in ovarian cancer.
IIn various ovarian cancer trials, typical ORR/PFS (Objective Response Rate/ Progression Free Survival) has been seen to be 15-20% and 3-4 months respectively. However, ovarian cancer patients can be sub-classified by their FR alpha expression as high, medium, and low. Immunogen's Mirvetuximab Soravtansine has been seen to be more potent in the sub-population of ovarian cancer patients with high or medium FR alpha. In a phase 1 trial it was seen that while overall ORR was similarly poor as in other drug trials, the sub-population ORR was double, at 44%. These are outstanding results and informs the phase 3 trial of mirva.
Ovarian cancer has been a major problem from a medicine point of view. Ovarian cancer ranks as the ninth most common cancer in women, the second most common gynecological cancer and first for the most deaths due to gynecological cancers. Trials have not produced outstanding results in the broad population. Few drugs have actually seen results that are highly differentiated from the median. One of the best known and most effective cancer drugs, Avastin, had only a 27% PFS initially, which went up to 54% in a second trial. There's hardly any question of OS in these trials, and ovarian cancer, which is hard to detect because there aren't many symptoms, kills 14,000 American women each year. Last year, a major trial supporting the use of the gruelling IP chemo process failed. Because of low early detection rates, lack of therapy, and complexity of the cancer, few trials of new drugs have succeeded in treating ovarian cancer.
The big problem with treating ovarian cancer, OvCa, is that it is considered not a single cancer but a multitude of different types of cancer. Thus it becomes very difficult to classify it properly and find common ground for a single drug to target the cancer. However, ovarian cancer patients almost always overexpress Folate receptors. What is interesting is that ovarian cancer patients can be classified by their Folate Receptor alpha (FRα) expression as low, medium and high based on the percent of tumor cells, 25-49%, 50-74%, and 75-100%, respectively. According to one study, "FRα is an attractive candidate for targeted biologic therapy of ovarian cancer. It is reported to be expressed in the majority of non-mucinous epithelial ovarian tumors at levels 10- to 100-fold higher than its normal expression in the kidney and on lung and breast epithelial cells. In addition, FRα is a tumor antigen, with 70% of women with ovarian or breast cancer showing measurable immune responses against this protein….We show that 134 of 186 (72%) primary tumors and 22 of 27 (81.5%) recurrent tumors were positive for FRα expression."
Immunogen's lead product candidate mirva showed unimpressive results in a broad population of patients with ovarian cancer. However, in a subgroup analysis, it was seen that for patients with high or medium FRα expression, ORR was at 44% - this was quite a bit more than the standard ORR, and was a great piece of trial result.
The Phase 1 cohort trial for "Mirvetuximab Soravtansine" had 46 patients and among them 23 had high, 14 had medium, and 9 had low expression of FRα and they all had previously received platinum and a taxane. In all the 46 patients, the confirmed ORR was 26% and median progression-free survival (NYSE:PFS) was 4.8 months. However, among them, in 16 patients who received up to three previous prescribed treatments and had high or medium FRα expression, the ORR was highest at 44% and median PFS was 6.7 months. For the other 30 patients with low FRα and who had received four or five previous prescribed treatments, ORR was 17% and median PFS was 4.2 months - which is somewhere in the higher end of the standard results, but not impressive. However, the 16-patient subpopulation with multiple previous treatments and high FRα produced pretty good results. Mirva thus proved to be more potent for patients with high level of FRα expression of tumor cell in platinum resistant ovarian cancer.
According to ImmunoGen's estimation 40% of ovarian cancer cases have high FRα expression, 20% have medium, 20% have low, and 20% have very low levels of FRα. There are approximately 22,500 cases of ovarian cancer patients in the US. Now, FRα high and medium is quite a large subgroup of ovarian cancer patients, occurring in some 60% of all such patients, which is now the target population for mirva.
ImmunoGen expects to report data from A phase 2 trial, FORWARD II, which looks at mirvetuximab soravtansine in combination with other treatments in the next quarter with data to be reported at the ASCO (American Society of Clinical Oncology) meeting in June. If mirvetuximab soravtansine works well in combination with currently approved drugs, such as Roche's Avastin and Merck's Keytruda, investors should have more confidence that mirvetuximab soravtansine will work on its own in later-stage patients who have failed other treatments.
ImmunoGen has faced some setbacks in 2016, and with tax loss selling pressure the stock is trading for less than $3 per share. The company ended the year with about $160 to $170 million in the bank and has a market cap of $215.63 million. The top institutional holders are ClearBridge Investments LLC, Orbimed Advisors LLC, Primecap Management Company etc.
Current treatment costs for ovarian cancer could be as high as $100,000 for first line of treatment. IMGN853 is single agent therapy for platinum resistant ovarian cancer. I see the price potential for IMGN853 could be around one third of the first line of treatment which is around $30,000. There are approximately 22,500 new cases of ovarian cancer patients in the US. Now 60% of this patient population of ovarian cancer patients with high or medium level of FRα expression is 13,500. Thus we get a market potential of about $400mn for IMGN853 if and when it succeeds in its NDA.
On the flipside, mirva is in very early stages of trial, and nothing is sanguine at this stage. We have seen myriad number of times how a drug that does well in preclinical and phase 1 stages fails in phase 3 trials. We have also seen flaws in subgroup analysis coming unhinged in larger trials, so the higher ORR in FRα subgroup may have a different explanation altogether. Finally, dilution; although the company does have quite a bit of cash, it may be another 2-3 years before an NDA is submitted, so this investment does come with some dilution risk. Investors must consider both sides of the coin before taking a call.
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I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.