biotickrImmunoGen Inc. is a clinical-stage biotechnology company focusing on the development of antibody-drug conjugate (ADC) as a treatment for cancer. The lead pipeline is mirvetuximab soravtansine, an inhibitor of folate-receptor alpha (FRa). The pipeline is in Phase III clinical trial to investigate the safety and efficacy against platinum-resistant ovarian cancer.
The next important pipeline is Pivekimab sunirine, a CD123-specific ADC for the treatment of acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm (Phase II). Two other pipelines such as IMGC936 and IMGN151 are in the pre-clinical stages
Platinum-resistant ovarian cancer (PROC) is a type of high-end treatment-resistant ovarian cancer that can unlikely treated by the existing standard-of-care treatment drugs. Limited clinical benefits and significant side effects impede the use of these drugs in PROC.
Mirvetuximab soravtansine (MIRV) is a first-in-class antibody-drug conjugate (ADC) comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent that has demonstrated significant anti-tumor activity in this difficult-to-treat population. MIRV, an antibody-drug conjugate, delivers the potent tubulin-target agent maytansinoid DM4 directly to the tumor in women with folate receptor (FR)-alpha-positive ovarian cancer.
According to a pooled analysis of 464 patients (pool of sub-group patients out of other PROC patients), MIRV monotherapy has unique efficacy and low-grade side effects including gastrointestinal and eye problems. According to IMGN, these side effects are manageable, highlighting the favorable risk/benefit in PROC patients.
While similar drugs failed to demonstrate efficacy in platinum-resistant ovarian cancer patients, Mirvetuximab consistently proved the efficacy. The possible reason for these two variable results might be – the competitor drug clinical trials like Farletuzumab failed to include patients with FRα expression; however, IMGN has included the patients expressing FRα in the tumors (proper patient selection).
A durable treatment response with a better safety profile was observed in combined therapy of MIRV and Bevacizumab in high folate receptor alpha recurrent ovarian cancer. The reported reduction in tumor burden was 97% with durable and rapid tumor shrinkage among PROC patients.
FRα is a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Its over-expression in tumors such as ovarian, breast, and lung cancers, low and restricted distribution in normal tissues, alongside emerging insights into tumor-promoting functions and association of expression with patient prognosis, together render FRα an attractive therapeutic target.
Theoretically, great drug but practically, the drug faced failure in the phase III study, and the second phase III clinical is being analyzed and demonstrated the efficacy based on sub-group analysis of patients, a study design that has a long history of failure to gain regulatory approval.
Even an investor with basic knowledge on clinical trials can see the flaws in the clinical trial study design such as
- The single group as treatment without a comparator arm or placebo group to demonstrate the efficacy as a comparison
- Open-label study or non-masked or blinded study – to reduce treatment bias, it is good to conduct a double-blinded study (neither patient nor investigator is aware whether the patient is taking treatment drug or placebo)
- A low number of patient recruitment – just 106 patients in phase III
- A high possibility (up to 60%) of repeat studies with a comparator group could be demanded by FDA
- In that case, IMGN could try to convince the FDA by showcasing the number of patients in the phase I study (206 patients) and the completed phase III study (366 patients)
- Risk of developing eye toxicity – blurred vision, keratopathy, etc, which are said to be reversible (it could be possibly worse and force the patients to discontinue the treatment)
Recent Activity
January 5th, 2023 – ImmunoGen announced inducement grants under Nasdaq listing Rule 5635(c)(4)
January 4th, 2023 – ImmunoGen appointed Michael Vasconcelles, MD, as Executive Vice President, Research, Development, and Medical Affairs
December 26th, 2022 – ImmunoGen announced a Webcast of Presentation and Q&A at the 41st Annual J.P. Morgan Healthcare Conference
December 10th, 2022 – ImmunoGen presented findings from expansion cohorts in Phase 1b/2 study of Pivekimab Sunirine with Vidaza® and Venclexta® in acute myeloid leukemia at ASH
Addressable Market
The highest unmet medical need in the cancer niche is platinum-resistant recurrent ovarian cancer. In fact, since the FDA approval of bevacizumab in 2014, no new agents hit the market. While the need to continue to push in both platinum-sensitive and platinum-recurrent diseases, the platinum-resistant disease have the highest unmet need.
The global market size of ovarian cancer was valued at USD1.8 billion in 2018 which will continue to increase by USD6.7 billion by 2028 at a CAGR of 14.4%
Current Finances
As of September 30th, 2022 IMGN had USD309.5 million in cash and cash equivalents. During the same period, the company generated USD15.4 million in revenue including USD8 million from non-cash royalty revenue and the rest from licensing and other milestone fees. The operating expenses were USD92.8 million.
Even though IMGN is currently unprofitable and not forecasted to be profitable over the next 3 years, the stock has returned 7.1% over the past year. IMGN is not significantly volatile over the past three months and remains stable. The company’s revenue is growing faster than the other stocks at the rate of 40.4% per year.
The total cash and short-term investment are USD 309.5 million. The long-term and other assets are equivalent to USD 29.8 million.
The short-term liabilities of USD103.6 million were exceeded by the short-term assets of USD330.4 million.
The long-term liabilities of USD77.2 million were exceeded by the long-term assets of USD330.4 million.
IMGN is debt-free and has an adequate cash runway for more than a year based on the free cash flow.
Insider Activity
Competitors
Genentech: Avastin® (bevacizumab)
Bevacizumab (approved in 2014) and it is the only drug available in the market, enjoying a monopoly in PROC market.
Summary
While the science of MIRV appears to be good, the drug failed to demonstrate reasonable efficacy in the late-phase clinical trials. The subgroup analysis could be the last resort, but retail twitter has mixed feelings about the outcome;
