ImmunoGen Announces Top-Line Results from Phase 3 FORWARD I Study of Mirvetuximab Soravtansine in Ovarian Cancer

On March 1, 2019 ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that its Phase 3 FORWARD I trial evaluating the safety and efficacy of mirvetuximab soravtansine compared to chemotherapy in patients with folate receptor alpha (FRα)-positive, platinum-resistant ovarian cancer did not meet its primary endpoint of progression-free survival (PFS) in either the entire study population or in the pre-specified subset of patients with high FRα expression (Press release, ImmunoGen, MAR 1, 2019, View Source [SID1234533865]).

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"Even though FORWARD I did not meet its primary endpoint, I continue to be impressed with the efficacy and tolerability of mirvetuximab soravtansine in ovarian cancer patients, especially in the subset with high FRα expression," said Dr. Kathleen Moore, Associate Director of Clinical Research at the Stephenson Cancer Center at the University of Oklahoma. "I look forward to continuing to work with ImmunoGen to analyze the Phase 3 data and determine the most appropriate path to bringing mirvetuximab soravtansine to those patients who benefit most from it."

The FORWARD I Phase 3 trial randomized 366 patients 2:1 to receive either mirvetuximab soravtansine or the physician’s choice of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel). Eligibility criteria included patients with platinum-resistant ovarian cancer that expressed medium or high levels of FRα who have been treated with up to three prior regimens. The primary endpoint of this study was PFS, which was assessed using the Hochberg procedure in the entire study population and in the subset of patients with high FRα expression. The Hochberg procedure enables the simultaneous testing of two overlapping populations. Under this statistical analysis plan, if the p-value of the primary endpoint in either population is greater than 0.05, the p-value in the other population needs to be less than or equal to 0.025 to achieve statistical significance.

"Based upon the efficacy signals we observed in the high FRα subset with PFS, confirmed overall response rate and overall survival, we are conducting additional analyses to further evaluate the potential benefit of mirvetuximab soravtansine for FRα-positive platinum-resistant ovarian cancer," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "We want to thank the patients who participated in this trial, the clinical investigators, and the support staff for their hard work, as we continue to pursue our goal of finding innovative cancer treatments for patients in need."

Key findings from FORWARD I are as follows:

In the entire study population, the confirmed overall response rate was higher for mirvetuximab soravtansine than for chemotherapy (22% vs 12%, p-value 0.015), without a significant difference in the primary endpoint of PFS (HR 0.98, p-value 0.897) or overall survival (HR 0.81, p-value 0.248).
In the pre-specified high FRα subgroup (218/366, 60%)
PFS was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.69, p-value 0.049). Given that the p-value in the entire study population exceeded 0.05, the statistical analysis plan for the study required the p-value in the high subset to be less than or equal to 0.025 to achieve statistical significance.
Confirmed overall response rate was higher for mirvetuximab soravtansine than for chemotherapy (24% vs 10%, p-value 0.014).
Overall survival was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.62, p-value 0.033).
Mirvetuximab soravtansine was well-tolerated, with fewer patients experiencing grade 3 or greater adverse events (46% vs 61%), fewer dose reductions (20% vs 31%), and fewer discontinuations due to drug-related adverse events (5% vs 8%) compared with chemotherapy.
The safety profile of mirvetuximab soravtansine was confirmed, with the most common adverse events including nausea (54% all grades; 2% grade 3 or greater), diarrhea (44% all grades; 4% grade 3 or greater), and blurred vision (43% all grades; 3% grade 3 or greater).
"This study with mirvetuximab did not result in the outcome that we had hoped for in platinum-resistant patients. We will further assess the data from FORWARD I to determine potential next steps with a monotherapy approach. In parallel, we have generated encouraging data with mirvetuximab combination regimens and will evaluate our ongoing studies as an independent path forward to support a registration in ovarian cancer," said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. "ImmunoGen is in a strong financial position with approximately $295 million in cash on our balance sheet, and we will continue to advance our portfolio of next-generation ADCs, which includes three additional development candidates targeting a range of tumor types in both hematologic malignancies and solid tumors."

ImmunoGen intends to present additional results from FORWARD I at an upcoming medical meeting.

CONFERENCE CALL INFORMATION
ImmunoGen will host a conference call on March 1, 2019 at 8 a.m. ET to discuss the top-line findings from the FORWARD I trial. To access the live call by phone, dial 334-323-0522; the conference ID is 7188781. The call may also be accessed through the "Investors and Media" section of the Company’s website, www.immunogen.com. Following the live webcast, a replay of the call will be available at the same location through March 15.

ABOUT FORWARD I
FORWARD I is a Phase 3 trial in which 366 patients were 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 were diagnosed with platinum-resistant ovarian cancer that expresses medium or high levels of FRα and were treated with up to three prior regimens. The primary endpoint of this study was progression free survival (PFS), which was assessed in the entire study population and in the subset of patients with high FRα expression. ImmunoGen estimates that 12,000-14,000 patients per year in the U.S. meet these criteria, with a comparable number in the major markets in Europe.

ImmunoGen partnered with the GOG Foundation Inc., a leader in clinical research in gynecologic malignancies, on FORWARD I, which was conducted in North America and Europe. This trial was intended to support full marketing approval of mirvetuximab soravtansine for patients with platinum-resistant ovarian cancer.

ABOUT MIRVETUXIMAB SORAVTANSINE
Mirvetuximab soravtansine (IMGN853) is the first folate receptor alpha (FRα)-targeting ADC. It uses 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.

Medtronic EVP & MITG President Bob White to Speak at Cowen Healthcare Conference

On March 1, 2019 Medtronic plc (NYSE:MDT), the global leader in medical technology, reported it will participate in the 39th Annual Cowen and Company Healthcare Conference on Monday, March 11, 2019, in Boston, Massachusetts (Press release, Medtronic, MAR 1, 2019, View Source;p=RssLanding&cat=news&id=2389717 [SID1234533863]).

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Bob White, executive vice president and president of Medtronic’s Minimally Invasive Therapies Group (MITG), will answer questions about the company beginning at 11:20 a.m. EDT (10:20 a.m. CDT).

A live audio webcast of the presentation will be available on March 11, 2019, by clicking on the Investor Events link at View Source An archive of the session will be available on the same webpage later in the day.

Medtronic EVP & CFO Karen L. Parkhill to Speak at Barclays Global Healthcare Conference

On March 1, 2019 Medtronic plc (NYSE:MDT), the global leader in medical technology, reported it will participate in the Barclays Global Healthcare Conference 2019 on Tuesday, March 12, 2019, in Miami, Florida (Press release, Medtronic, MAR 1, 2019, View Source;p=RssLanding&cat=news&id=2389729 [SID1234533862]).

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Karen Parkhill, executive vice president and chief financial officer of Medtronic, will answer questions about the company beginning at 9:00 a.m. EDT (8:00 a.m. CDT).

A live audio webcast of the presentation will be available on March 12, 2019, by clicking on the Investors Events link at View Source An archive of the session will be available on the same webpage later in the day.

Portola Pharmaceuticals Reports Fourth Quarter and Full Year 2018 Financial Results and Provides Corporate Update

On March 1, 2019 Portola Pharmaceuticals, Inc. (Nasdaq: PTLA) reported financial results for the three and twelve months ended December 31, 2018 and provided a corporate update (Press release, Portola Pharmaceuticals, MAR 1, 2019, View Source;p=RssLanding&cat=news&id=2389690 [SID1234533860]).

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"Today’s positive opinion on Ondexxya from the Committee for Medicinal Products for Human Use (CHMP) builds upon the momentum established in 2018, which included the U.S. Food and Drug Administration (FDA) approval of our breakthrough-designated, Factor Xa inhibitor reversal agent Andexxa, followed by three consecutive quarters of strong revenues and the approval of our Generation 2 manufacturing process. We also continued the build-out of our experienced leadership team and advanced our Syk/JAK inhibitor cerdulatinib," said Scott Garland, Portola’s president and chief executive officer. "With the full commercial launch of Andexxa now underway in the United States, the pending approval from the European Commission anticipated in early May, and the further extension of our cash runway, we look forward to continuing our positive momentum through 2019."

Quarter Ending Dec. 31, 2018 and Full Year 2018 Financial Results

Total revenues for the fourth quarter of 2018 were $15.3 million, compared with $9.8 million for the fourth quarter of 2017. This includes $14.0 million in net product revenues from Andexxa sales, $35 thousand in revenues from Bevyxxa sales and $1.2 million in collaboration and license revenues. Total revenues for the full year 2018 were $40.1 million, compared with $22.5 million for the full year 2017. Please see the tables at the end of this press release for a detailed breakdown of revenues.

Net loss attributable to Portola, according to generally accepted accounting principles in the U.S. (GAAP), was $88.5 million for the fourth quarter of 2018, or $1.34 net loss per share, compared with a net loss of $91.8 million, or $1.41 net loss per share, for the same period in 2017. Net loss for the full year 2018 was $350.2 million, or $5.31 net loss per share, compared with a net loss of $286.1 million, or $4.81 net loss per share, for the full year 2017. This includes the effect of two charges taken in the fourth quarter of 2018 related to the FDA approval for the Company’s Gen 2 manufacturing process. The first is a $9.2 million charge associated with the valuation of the Company equity that will be issued to Lonza, our Andexxa Gen 2 manufacturer ("manufacturing site charge"), and the second is a $10.3 million charge associated with the Andexxa Gen 1 product as hospitals transition to the Gen 2 product ("Gen 1 supply charge").

Non-GAAP net loss for the fourth quarter of 2018 was $69.0 million, or a non-GAAP basic and diluted loss per share of $1.04. For the full year 2018, non-GAAP net loss was $330.7 million, or non-GAAP basic and diluted loss per share of $5.01. Non-GAAP net loss and loss per share have been adjusted to remove the manufacturing site charge and the Gen 1 supply charge. Please see the reconciliation of GAAP to non-GAAP financial measures at the end of this release for more details.

Cash, cash equivalents and investments at December 31, 2018 totaled $317.0 million, compared with $534.2 million as of December 31, 2017.

Total operating expenses for the fourth quarter of 2018 were $102.5 million, compared with $95.7 million for the same period in 2017. Total operating expenses for the full year 2018 were $385.5 million, compared with $295.2 million for the full year 2017. This year-over-year increase was driven by the Company’s Gen 2 manufacturing expenses, the build-out of the Company’s field force, as well as the two charges outlined above in the fourth quarter.

Non-GAAP total operating expenses, which excludes the two charges outlined above, were $83.0 million for the fourth quarter of 2018, and $365.9 million for the full year 2018. Please see the reconciliation of GAAP to non-GAAP financial measures table at the end of this release for more details.

Stock-based compensation expense for the fourth quarter of 2018 was $19.8 million, compared with $10.9 million for the same period in 2017. Stock-based compensation expense for the full year 2018 was $55.4 million, compared with $43.3 million for the full year 2017. This year-over-year increase was driven mainly by the manufacturing site charge.

Cost of Sales (COS) for the fourth quarter of 2018 were $12.4 million, compared to $260 thousand for the same period in 2017. COS for the full year 2018 were $18.1 million, compared to $415 thousand for the same period in 2017. This year-over-year increase was driven by the launches of Andexxa and Bevyxxa, and the Gen 1 supply charge.

Research and development (R&D) expenses were $49.5 million for the fourth quarter of 2018, compared with $68.5 million for the fourth quarter of 2017. The decrease was driven primarily by the timing of manufacturing costs for Andexxa Gen 2 campaigns. R&D expenses were $216.2 million for the full year 2018, compared with $203.7 million for the full year 2017. This year-over-year increase was driven by expenses related to Andexxa Gen 2 manufacturing.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2018 were $40.6 million, compared with $26.9 million for the same period in 2017. SG&A expenses for the full year 2018 were $151.2 million, compared with $91.1 million for the full year 2017. These increases were driven by the hiring of the Company’s field force to support the launches of Andexxa and Bevyxxa.
2019 Annual Financial Guidance
For the fiscal year 2019, Portola expects total R&D expenses to be between $125 million and $140 million, including stock-based compensation of approximately $22 million. Portola expects total SG&A expenses to be between $200 million and $215 million, including stock-based compensation expenses of approximately $36 million. These operating expenses are primarily for ongoing clinical trials, potential label enhancing studies for Andexxa, and support for the commercial launch of Andexxa in the U.S and launch activities in Europe.

Recent Achievements and Events

Received positive opinion on Ondexxya from CHMP.
Signed $125 million loan agreement with HealthCare Royalty Partners and Athyrium Capital Management.
Published full ANNEXA-4 study results in The New England Journal of Medicine following presentation of results at the International Stroke Conference (ISC) 2019.
Appointed 30+-year industry veteran Sheldon Koenig as chief commercial officer.
Completed cerdulatinib end-of-phase-2 meeting, which provided guidance on regulatory pathway for a peripheral T-cell lymphoma (PTCL) registrational study that is anticipated to begin by year-end.
Initiated broad U.S. launch of Andexxa following FDA approval of Gen 2 supply, and expanded sales force by approximately 40 representatives.
Upcoming Milestones

Anticipated receipt of C-code from The Centers for Medicare & Medicaid Services, allowing hospitals an additional reimbursement pathway for Andexxa.
European Commission decision on the marketing authorization application for Ondexxya expected in early May 2019.
Initiate discussions with the FDA on a number of potential label expansion opportunities including the addition of the ANNEXA-4 efficacy data, the inclusion of edoxaban and enoxaparin, and the potential initiation of a study in urgent surgery.
Conference Call Details
Portola will host a conference call today, Friday, March 1, 2019, at 8:30 a.m. ET, during which time management will discuss the fourth quarter and full year 2018 financial results, updates on the U.S. launch of Andexxa, and other matters. The live call can be accessed by phone by dialing (844) 452-6828 from the U.S. and Canada or 1 (765) 507-2588 internationally and using the passcode 6999805. The webcast can be accessed live on the Investor Relations section of the Company’s website at View Source It will be archived for 30 days following the call.

Use of Non-GAAP Financial Measures
This press release and the reconciliation table included herein include non-GAAP net loss, non-GAAP basic and diluted loss per share and non-GAAP operating expenses. The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the company’s financial condition and results of operations. When viewed in conjunction with GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those that the Company uses as a basis for evaluating performance, allocating resources and planning and forecasting future periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation of GAAP to non-GAAP financial measures is provided in the accompanying table entitled "Reconciliation of GAAP to Non-GAAP Financial Measures."

TG Therapeutics Announces Approximately $85 million in Equity and Debt Financings

on March 1, 2019 TG Therapeutics, Inc. (NASDAQ: TGTX), a biopharmaceutical company developing medicines for patients with B-cell mediated diseases, reported approximately $85 million in equity and debt financing (Press release, TG Therapeutics, MAR 1, 2019, View Source [SID1234533859]).

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The Company priced a public offering of its common stock for gross proceeds of approximately $25.2 million, before deducting underwriting discounts and commissions and offering expenses payable by the Company. In addition, the Company granted the underwriters a 30-day option to purchase $3.8 million of additional shares of common stock. All of the shares in the offering are being sold by the Company. The Company anticipates using the net proceeds from the offering to fund the ongoing development of ublituximab and umbralisib, for research and development activities and for general corporate purposes. The offering is expected to close on March 5, 2019 subject to customary closing conditions.

Cantor Fitzgerald & Co. acted as the sole book-running manager for the offering. The underwriter may offer the shares from time to time for sale in one or more transactions on The NASDAQ Capital Market, in the over-the-counter market, through negotiated transactions or otherwise at market prices prevailing at the time of sale, at prices related to prevailing market prices or at negotiated prices. On February 28, 2019, the last sale price of the shares as reported on The NASDAQ Capital Market was $6.80 per share.

In addition to the above equity financing, the Company also announced yesterday that it has secured a $60 million venture debt facility with Hercules Capital, a leader in customizing debt financing for companies in the life sciences and technology-related markets.

The shares of common stock described above are being offered by the Company pursuant to its shelf registration statement on Form S-3 previously filed with the Securities and Exchange Commission (SEC) on May 26, 2017 and declared effective by the SEC on June 13, 2017. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s web site at www.sec.gov. Copies of the final prospectus supplement, when available, and accompanying prospectus relating to these securities may also be obtained by sending a request to: Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 6th Floor New York, New York 10022; email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.