On May 18, 2021 Novocure (NASDAQ: NVCR) reported the U.S. Food and Drug Administration (FDA) has approved the company’s Investigational Device Exemption (IDE) supplement, reducing the enrollment requirement for its LUNAR trial to 276 patients with 12 months follow-up (Press release, NovoCure, MAY 18, 2021, View Source [SID1234580220]). LUNAR is a phase 3 pivotal trial testing the effectiveness of Tumor Treating Fields in combination with immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone for patients with stage 4 NSCLC who progressed during or after platinum-based therapy.

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The IDE supplement incorporates recommended changes from the interim analysis of the LUNAR trial conducted by an independent data monitoring committee (DMC). After review of the interim analysis report earlier this year, the DMC concluded that the LUNAR trial should continue with no evidence of increased systemic toxicity. The DMC also stated that it is likely unnecessary and possibly unethical for patients randomized to the control arm of the trial to continue accrual according to the original protocol. The DMC recommended a reduced sample size of approximately 276 patients with 12 months follow-up which it believes will provide sufficient overall power for both primary and secondary endpoints. The DMC recommended no other changes to the trial design. Novocure remains blinded to all data.

"We are very pleased with the FDA approval of the DMC’s recommended protocol adjustments and are grateful for the FDA’s prompt review," said Asaf Danziger, Novocure’s CEO. "We now anticipate last patient enrollment in the LUNAR trial in the fourth quarter of 2021 with final data available in 2022 and look forward to sharing data from the LUNAR trial as quickly as possible."

About LUNAR

LUNAR is a phase 3 pivotal trial testing the effectiveness of TTFields in combination with immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone for patients with stage 4 NSCLC who progressed during or after platinum-based therapy. It is estimated that approximately 46,000 patients receive second-line treatment for stage 4 NSCLC each year in the U.S. The primary endpoint is superior overall survival of patients treated with TTFields plus immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone. TTFields is intended principally for use in combination with other standard-of-care treatments, and LUNAR was designed to generate data that contemplates multiple outcomes, all of which Novocure believes will be clinically meaningful.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a broad range of clinical trials across all phases, included four phase 3 pivotal trials in a variety of tumor types. To date, more than 18,000 patients have been treated with TTFields.

Use of Tumor Treating Fields for the treatment of NSCLC is investigational only.

On May 18, 2021 Bristol Myers Squibb (NYSE: BMY) reported that the company will participate in a fireside chat at the UBS Global Healthcare Virtual Conference, which will be webcast on Tuesday, May 25, 2021 (Press release, Bristol-Myers Squibb, MAY 18, 2021, View Source [SID1234580188]). David Elkins, Executive Vice President, Chief Financial Officer and Samit Hirawat, M.D., Executive Vice President, Chief Medical Officer, Global Drug Development, will answer questions about the company at 1 p.m. ET.

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Investors and the general public are invited to listen to a live webcast of the session at View Source An archived edition of the session will be available later that day.

On May 18, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported receipt of regulatory feedback from the U.S. Food and Drug Administration (FDA) regarding its potency assays for lifileucel (Press release, Iovance Biotherapeutics, MAY 18, 2021, View Source [SID1234580205]). Previously, the company reported the submission of assay data to the FDA and recently the FDA provided comments regarding the data package.

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Following FDA feedback, Iovance will continue its ongoing work developing and validating its potency assays and plans to submit additional assay data and to meet with the FDA in the second half of 2021. The company’s biologics license application (BLA) submission for lifileucel is now expected to occur during the first half of 2022.

"TIL is a first-in-class, one-time administration cell therapy and the first potential BLA for a cell therapy in solid tumors," stated Maria Fardis, Ph.D., MBA, Iovance President and Chief Executive Officer. "As such, TIL product is complex by nature and alignment with FDA on a potency assay is an important step toward BLA submission. With a regenerative medicines advanced therapy (RMAT) designation for lifileucel, FDA recognizes the unmet need for patients with metastatic melanoma who progress after anti-PD1 therapy."

On May 18, 2021 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications reported its unaudited financial results for the first quarter of 2021 (Press release, Legend Biotech, MAY 18, 2021, View Source [SID1234580221]).

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"We built on the momentum of 2020 during the first quarter of this year for our BCMA CAR-T therapy cilta-cel with our collaboration partner, Janssen Biotech, Inc.*(Janssen), completing the Biologics License Application to the U.S. FDA and the Marketing Authorisation Application to the EMA," said Ying Huang, PhD, CEO and CFO of Legend Biotech. "We look forward to an exciting year with new and updated data from the CARTITUDE clinical development program and reaching our goal of bringing a new CAR-T treatment option to patients living with multiple myeloma worldwide pending regulatory approvals."

*In December 2017, Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. to develop and commercialize cilta-cel.

First Quarter 2021 & Recent Highlights

In the first quarter of 2021, the rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) was completed by Legend Biotech’s collaborator, Janssen, for cilta-cel, for the treatment of adults with RRMM.
On April 30, 2021 the Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) was made by Legend Biotech’s collaborator, Janssen, for cilta-cel for the treatment of adults with RRMM. This follows the granting of an accelerated assessment for this MAA by the EMA’s Committee for Medicinal Products for Human Use (CHMP) in February 2021.
On May 13, 2021, Legend Biotech entered into a subscription agreement with an institutional investor for the offer and sale of 20,809,805 ordinary shares in a private placement at a purchase price of $14.41625 per ordinary share (equivalent to $28.8325 per American Depositary Share, or ADS) and the issuance of a warrant exercisable for up to an aggregate of 10,000,000 ordinary shares, exercisable for a two-year period at an exercise price of $20.00 per ordinary share (equivalent to $40.00 per ADS).
Key Upcoming Milestones

Updated clinical data, including longer term follow up results from the CARTITUDE-1 trial, will be presented at the virtual 2021 ASCO (Free ASCO Whitepaper) Annual Meeting taking place on June 4-8 , 2021 (oral presentation, abstract #8005) along with initial data from the CARTITUDE-2 trial (abstracts #8013, #8028). In addition, there will be three poster presentations featuring real-world data (abstracts #8045, #8030 and #8041).
Nine abstracts will be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress taking place virtually on June 9-17, 2021. (abstracts #S190, #EP964, #EP1003, #EP987, #EP990, #EP1049, #EP978, #EP977 and #EP972).
Legend Biotech intends to use the data from the CARTIFAN-1 study in support of a regulatory submission to the China Center for Drug Evaluation (CDE) in the second half of 2021 seeking approval of cilta-cel for the treatment of adults with RRMM.
Legend Biotech’s collaboration partner, Janssen, anticipates submitting a New Drug Application (NDA) to the Japan Ministry of Health, Labor and Welfare (JMHLW) in the second half of 2021 seeking approval of cilta-cel for the treatment of adults with RRMM.
Legend Biotech expects to initiate its Phase 1 clinical trial of LB1901 in RR T-cell lymphoma (TCL) in the United States in 2021.
Legend Biotech anticipates supporting investigators with publishing a clinical data update from LEGEND-2 study in 2021.
Financial Results for First Quarter Ended March 31, 2021

Cash and Cash Equivalents and Time Deposits

As of March 31, 2021, Legend Biotech had approximately $412.3 million of cash and cash equivalents and approximately $50.0 million in time deposits.

Revenue

Revenue for the three months ended March 31, 2021 was $13.7 million compared to $11.5 million for the three months ended March 31, 2020. The increase of $2.2 million was primarily due to revenue recognition of additional milestone payment achieved pursuant to Legend Biotech’s agreement with Janssen. Milestone payments are constrained as a result of the uncertainty of whether the milestone will be achieved, but recognized when the associated milestone is achieved and the uncertainty relieved. In the first quarter of 2021, this resulted in a larger amount of revenue recognized from the contract liabilities. Legend Biotech has not generated any revenue from product sales to date.

Research and Development Expenses

Research and development expenses for the three months ended March 31, 2021 were $71.1 million compared to $48.0 million for the three months ended March 31, 2020. This increase of $23.1 million was primarily due to a higher number of clinical trials with more patients enrolled and a higher number of research and development product candidates.

Administrative Expenses

Administrative expenses for the three months ended March 31, 2021 were $8.7 million compared to $3.4 million for the three months ended March 31, 2020. The increase of $5.3 million was primarily due to Legend Biotech’s expansion of supporting administrative functions to aid continued research and development activities.

Selling and Distribution Expenses

Selling and distribution expenses for the three months ended March 31, 2021 were $13.4 million compared to $6.5 million for the three months ended March 31, 2020. This increase of $6.9 million was primarily due to increased costs associated with commercial preparation activities for cilta-cel.

Other Income and Gains

Other income and gains for the three months ended March 31, 2021 was $0.7 million compared to $2.5 million for the three months ended March 31, 2020. The decrease of $1.8 million was primarily due to lower government grant and interest income received in first quarter of 2021.

Other Expenses

Other expenses for the three months ended March 31, 2021 was $2.0 million compared to $0.05 million for the three months ended March 31, 2020. The increase was primarily due to higher foreign currency exchange loss in first quarter of 2021.

Finance Costs

Finance costs for the three months ended March 31, 2021 was $0.04 million compared to $4.0 million for the three months ended March 31, 2020. The decrease was primarily due to finance costs related to the issuance of convertible redeemable preferred shares in 2020, which were fully converted into ordinary shares upon the completion of Legend Biotech’s initial public offering in June 2020.

Loss for the Period

For the three months ended March 31, 2021, net loss was $80.9 million, or $0.30 per share, compared to a net loss of $44.2 million, or $0.22 per share, for the three months ended March 31, 2020.

On May 18, 2021 Outpace reported that the company is taking cell and gene control technology originally in-licensed by Lyell out of that company’s toolbox and into a broad partnering model it thinks could transform the field (Press release, Outpace Bio, MAY 18, 2021, View Source [SID1234637772]).

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Outpace Bio Inc. launched in March with a $30 million series A round led by Artis Ventures and Lyell Immunopharma Inc., with participation by Abstract Ventures, Civilization Ventures, Mubadala Capital, Playground Global, Sahsen Ventures and WRF Capital.

The company’s leadership and scientific teams include inventors of de novo protein design technology developed at University of Washington’s Institute for Protein Design (IPD), many of whom joined Lyell when their inventions were brought under the well-funded cancer cell therapy company’s roof. That IP is now assigned to Outpace.

"The reason we’re spinning out from Lyell is that even massively capitalized companies can’t chew on all the hypotheses we want to address while moving at full speed on internal clinical development," said Outpace co-founder and CEO Marc Lajoie. "We have a lot to offer the field, and Lyell will benefit from that."

Outpace is developing "a whole platform of control modalities" to program cell and gene therapies for greater potency and safety, said Lajoie.

That includes synthetic biology strategies using "AND" or "NOT" Boolean logic gates to recruit or exclude signaling molecules to specific subcellular locations, control protein turnover, or require a specific combination of signals to unlock a desired function.

By designing fit-for-purpose proteins that don’t exist in nature, the company can go beyond standard strategies that manipulate expression of individual genes.

"First-generation approaches have been mainly focused on over-expressing this gene, or knocking out that gene," which can face limitations when a gene is integral to cell function in one setting but hampers it in another, said Lajoie. In contrast, he said, working at the protein level gives Outpace the ability to introduce desired changes in more context-specific ways.

Rather than develop its own pipeline, which would require investing in clinical development, the company is partnering with others to develop products via milestone- and royalty-driven deals. "The opportunity here is to create a step change in the field, and to be able to do that, we needed to focus our efforts on early development," Lajoie said.

In some cases, Outpace and the partner company will jointly design the program from the bottom-up, while in others, the partner will come to Outpace and use the company’s existing technology to solve a specific problem in an ongoing program, said co-founder and CSO Scott Boyken.

While the products developed through collaborations will belong to the partner companies, the underlying control technologies developed through the process belong to Outpace. "We can leverage our progress on the products we’re working on to increase our efficiency for other projects in the future," Lajoie said.

Outpace’s most advanced program is a collaboration with Lyell to develop cell therapies with controlled expression of an undisclosed cytokine. Other programs in development include a CAR cell therapy resistant to exhaustion, and a strategy for drug-induced gene regulation; the partnering status of these programs is undisclosed.

Lajoie said that while Outpace’s technology can be applied to any cell or gene therapy, the company’s "sweet spot" is T cell therapies for cancer.

Lajoie and Boyken co-authored a 2020 Science study with Fred Hutchinson Cancer Research Center professor Stanley Riddell showing the Co-LOCKR (Colocalization-dependent Latching Orthogonal Cage/Key pRoteins) technology they developed, part of Outpace’s IP portfolio, directed T cells to kill target cells expressing precise combinations of cell surface antigens, opening the door to more selective tumor targeting.

"There’s no single antigen that really distinguishes cancer cells from healthy cells, but there are aberrant combinations of antigens. That’s the unique handle we really wanted to pursue in that collaboration," said Lajoie.

He believes the series A round will give the company approximately three years of runway.

At least two other companies have been founded to develop synthetic biology control mechanisms for partners’ cell therapies.

Cell Design Labs Inc. was acquired by Gilead Sciences Inc. (NASDAQ:GILD) for $175 million up front and $322 million in total milestones after Gilead’s 2017 acquisition of Cell Design Labs’ partner, Kite Pharma Inc. The University of California San Francisco spinout, which raised $34.4 million in venture funds, developed technology to control CAR T cell function; its UCSF founders published two Science Translational Medicine studies on the technology last month.

Senti Biosciences Inc., which raised a $105 million series B round in January and a $53 million A round in 2018, has both a pipeline strategy and a partnering model.