Notch co-founder Juan Carlos Zúñiga-Pflücker, PhD.

Allogene Therapeutics will partner with Notch Therapeutics to research and develop induced pluripotent stem cell (iPSC) AlloCAR™ therapies for initial blood cancer indications that include non-Hodgkin lymphoma, leukemia, and multiple myeloma, the companies said today, through an exclusive worldwide collaboration and license agreement that could generate more than $300 million for Notch.

Under their partnership, Allogene and Notch plan to create allogeneic cell therapy candidates from T cells or natural killer (NK) cells using Notch’s Engineered Thymic Niche (ETN) platform, created to offer potential flexibility and scalability for the production of stem cell-derived immune cell therapies.

ETN is designed to enable the expansion of induced pluripotent stem cells (iPSCs) and differentiation of iPSCs from mature immune cells in scalable, fully defined, feeder-free and serum-free cultures into T cells that can be genetically tailored for any T cell-based immunotherapeutic application.

The platform uses genetically tailored stem cells as a renewable source for creating allogeneic T cell therapies that are designed, according to Notch, to deliver safer, consistently manufactured, and more cost-effective cell immunotherapies to patients.

“Master cell banks of genetically modified, induced pluripotent stem cells could provide an inexhaustible source of cell therapies that may improve outcomes and expand applicability to new areas,” said Notch co-founder Juan Carlos Zúñiga-Pflücker, PhD, a senior scientist at Sunnybrook Research Institute and a professor and chair of the department of immunology at the University of Toronto.

The ETN platform was developed in the labs of Zúñiga-Pflücker and another pioneer in iPSC and T cell differentiation technology, Peter Zandstra, PhD, FRSC, at the University of Toronto. The university and Sunnybrook joined with two other Toronto institutions, MaRS Innovation (now Toronto Innovation Acceleration Partners) and the Center for Commercialization of Regenerative Medicine (CCRM), to commercialize the technology last year by launching Notch, an immune cell therapy company creating universally compatible, allogeneic T cell therapies for the treatment of diseases of high unmet medical need.

Notch and Allogene reason that iPSCs may provide renewable starting material for Allogene’s allogeneic chimeric antigen receptor T cell (AlloCAR T™) cancer therapies, which are designed to allow for improved efficiency of gene editing, greater scalability of supply, product homogeneity, and more streamlined manufacturing.

Looking beyond cancer

“This work with Allogene may also pave the way for additional off-the-shelf cell therapeutics that are custom-designed to treat other immunity-related diseases such as infectious diseases, autoimmune diseases, and aging,” added Zandstra, who is also a Notch co-founder and the company’s CSO, as well as a professor at the University of British Columbia.

Notch has agreed to oversee preclinical research of next-generation iPSC AlloCAR T cells, while Allogene will clinically develop the product candidates and holds exclusive worldwide rights to commercialize the resulting products, the companies said.

Allogene has agreed to pay Notch $10 million upfront, up to $7.25 million tied to achieving research milestones, up to $4 million per exclusive target tied to achieving preclinical development milestones, and up to $283 million per exclusive target and cell type upon achieving clinical, regulatory, and commercial milestones. Allogene also agreed to pay Notch tiered royalties on net sales in the mid to high single digits.

Allogene is a South San Francisco, CA, cancer-fighting startup that was launched in April 2018 with Pfizer’s lead allogenic chimeric antigen receptor T-cell (CAR-T) candidate UCART19, licensed from Servier, and 16 preclinical CAR-T candidates licensed from Servier and Cellectis.

Allogene holds U.S. rights to two Phase I candidates: UCART19 for relapsed/refractory acute lymphoblastic leukemia (ALL), and ALLO-501 for relapsed/refractory non-Hodgkin lymphoma (NHL). The company expects to advance UCART19 into potential Phase II registrational trials in 2020, and read out data from ALLO-501 in the first half of next year.

No. 2 immuno-oncology startup

Allogene went public in October 2018, raising $372.6 million through its initial public offering—part of the total $792.8 million in capital raised by the company, catapulting it to No. 2 in GEN’s A-List of Top 10 Immuno-Oncology Startups, published February 25.

Allogene joined Notch to announce the partnership the same day that it reported third-quarter results. Allogene finished Q3 with a net loss of $50.7 million, up from a $43.5 million net loss in the year-ago quarter. The company reported $601.9 million in cash, cash equivalents, and investments as of September 30, down about 17% from $721.35 million as of December 31, 2018.

Yesterday, Canaccord Genuity initiated coverage of Allogene with a “Buy” rating: “We believe ALLO’s approach to allogeneic CAR-Ts has the potential to succeed in being the initial market leader in the allogeneic cell therapy space, providing high unmet need oncology patients with first-to-market allogeneic T-cell therapy products,” analyst John Newman, PhD, wrote.

Separately, Allogene has acquired a 25% equity position in Notch and will assume one seat on Notch’s Board of Directors.

“The scientific founders of Notch Therapeutics are among the most respected experts in the field of stem cell biology and its applications to generating T cells and other functional immune cells. We are confident that their technology and expertise, combined with Allogene’s leadership in AlloCAR therapies, has the potential to unlock future generations of cell therapy treatments for patients,” stated David Chang, MD, PhD, Allogene’s president, CEO, and co-founder.

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