Waltham, Massachusetts, based ImmunoGen, expanding field of antibody-drug conjugates (ADCs) with the development of the next generation of targeted anti-cancer agents, has completed an in-depth operational review designed to extend the company’s cash runway and deliver on its commitment to develop next-generation ADCs.

Based on the outcomes of this review, ImmunoGen will prioritize continued development of mirvetuximab soravtansine (IMGN853), the company’s first folate receptor alpha (FRα)-targeting ADC, using a humanized FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, DM4, to kill the targeted cancer cells.

In addition, the company said it will also continue to develop a select portfolio of three earlier-stage product candidates targeting solid tumors and hematological malignancies.

According to financial statements, Immunogen will end the current quarter with approximately US $240 million on its balance sheet and expects this cash, together with expense reductions resulting from the operational changes announced today and anticipated cash receipts from partners, will fund operations through the release of top-line results from the upcoming mirvetuximab soravtansine Phase III study in platinum-resistant ovarian cancer, which are expected in the first half of 2022.

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Failed to meet primary endpoint
The operational review commenced following the announcement that FORWARD I, ImmunoGen’s Phase III clinical trial evaluating mirvetuximab soravtansine compared to chemotherapy in women with folate receptor alpha (FRα)-positive, platinum-resistant ovarian cancer, did not meet the primary endpoint.

Data from FORWARD I did, however, demonstrate a consistent efficacy signal across a range of parameters in the pre-specified subset of patients with high FRα expression. Following consultation with the U.S. Food and Drug Administration (FDA), ImmunoGen will pursue a new Phase III study in this patient population. [1]

FORWARD I trial randomized 366 patients 2:1 to receive either mirvetuximab soravtansine or the physician’s choice of single-agent chemotherapy, which included pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel. Eligible patients diagnosed with platinum-resistant ovarian cancer that expressed medium or high levels of FRα and were treated with up to three prior regimens.

The established primary endpoint of this study was progression free survival (PFS), which was to be assessed in the entire study population and in the subset of patients with high FRα expression.

ImmunoGen partnered with the GOG Foundation, a leader in clinical research in gynecologic malignancies, on FORWARD I, which was conducted in North America and Europe. [1]

Strategic Goals
In light of these developments and with the goal of extending the it’s existing cash runway, ImmunoGen has established three strategic priorities for the business. These priorities, announced in a conference call on Thursday, include the execution of a registration study for mirvetuximab soravtansine in platinum-resistant ovarian cancer; advance a select portfolio of earlier-stage product candidates; and strengthen its balance sheet through partnering.

Consistent with these priorities, ImmunoGen will

  • Initiate the registration study for mirvetuximab soravtansine as a monotherapy for women with FRα-high, platinum-resistant ovarian cancer by the end of this year;
  • Complete enrollment and continue follow up in the ongoing FORWARD II mirvetuximab soravtansine combination cohorts;
  • Continue IMGN632 development in patients with relapsed acute myeloid leukemia (AML), blastic plasmacytoid dendritic cell neoplasm (BPDCN), and other CD123-positive hematologic malignancies in collaboration with Jazz Pharmaceuticals;
  • Advance two additional assets that demonstrate ImmunoGen’s continued innovation in ADCs: IMGC936, which is in co-development with MacroGenics with an IND expected by the end of 2019; and the company’s next generation anti-FRα ADC, which is expected to enter development in mid-2020; and
  • Monetize its remaining portfolio and platform technologies through out-licensing transactions or asset sales.

One of the priorities include the completion of the enrollment and continued follow up of the FORWARD II Phase Ib/II study of mirvetuximab soravtansine in combination with bevacizumab (Avastin®, Genentech/Roche), carboplatin or pembrolizumab (Keytruda®, Merck/MSD) in patients with FRα-positive platinum-resistant or platinum-agnostic ovarian cancer, primary peritoneal, or fallopian tube tumors, as well as a triplet combination of mirvetuximab soravtansine plus carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer.

Reducing costs
In order to reduce ongoing expenses, ImmunonGen, during the investor conference call, said that it will

  • Discontinue the development of IMGN779 in adults with relapsed/refractory CD33-positive AML;
  • Suspend all other research activities;
  • Reduce its workforce by approximately 220 employees (approximately 75% of it’s current workforce), with a majority of these employees separating from the business by mid-July 2019; and
  • Seek to sub-lease excess office and lab space.

Expected savings
Following a transition period, the savings generated by the restructuring are expected to reduce ImmunoGen’s quarterly expenses by more than 50%. As a result of the workforce reduction, the Company expects to record a one-time charge totaling approximately $16.4 million related to termination benefits and other related expenses. This charge is expected to be recorded in the quarter ending June 30, 2019, and the related cash payments will be substantially paid out by June 30, 2020. In addition, an anticipated charge of $3.7 million is expected to be incurred for retention benefits in the same time period. Updated 2019 financial guidance will be provided when ImmunoGen announces it second quarter operating results on August 2,2019.

“I thank the employees separating from the business for their significant contributions to ImmunoGen and to the advancement of the ADC field,” said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer.

“Reorganizing the business is critical to ImmunoGen’s future, enabling us to extend our cash position and continue the development of mirvetuximab soravtansine and our portfolio of promising ADCs in earlier stages of development. We look forward to continued progress with the business, including the start of the registration study for mirvetuximab soravtansine by year-end and additional monotherapy and combination data at the annual meeting of the European Society of Medical Oncology (ESMO) in September (2019), identifying a recommended Phase II dose and initiating combination studies with IMGN632 in the second half of the year, and filing an IND for IMGC936 by the end of 2019.”

Difficult decision
“This was an extremely difficult decision for the Board, as we believe deeply in the therapeutic promise of ADCs, the company’s science, and its people,” said Steve McCluski, ImmunoGen’s Chairman of the Board.

“These are, however, the right steps to take to bring mirvetuximab soravtansine to patients and offer the best opportunity to capture long-term value for our shareholders, whom we thank for their support,” McCluski concluded.

[1] Phase III Study of Mirvetuximab Soravtansine vs Investigator’s Choice of Chemotherapy in Women With FRa+ Adv. EOC, Primary Peritoneal or Fallopian Tube Cancer (FORWARD I). NCT02631876

[2] Study of Mirvetuximab Soravtansine in Comb. With Bevacizumab, Carboplatin, PLD, Pembrolizumab, or Bevacizumab + Carboplatin in Adults With FRa + Adv. EOC, Primary Peritoneal or Fallopian Tube Cancer (FORWARD II) NCT02606305

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