Shoreline Launches into Era of Cell Therapy with $4 Billion in Partnerships

Shoreline Biosciences, an immunotherapy company formed in 2020 during the early days of the COVID-19 pandemic, was propelled into the proverbial catbird’s seat this summer with two mega-deals, and now plans to double its employee base from 50 to 100 in the coming six to nine months.

Shoreline Biosciences is developing an off-the-shelf, targeted, allogeneic approach to natural killer (NK) and macrophage cell therapies, which Kleanthis G. Xanthopoulos, Ph.D., chairman and CEO, believes is one-of-a-kind.

This summer’s deals with Kite Pharmaceuticals, a Gilead Company, and BeiGene – totaling $4 billion and boasting combined upfront payments of over $120 million to further develop its induced pluripotent stem cell (iPSC) programs – are potent validation of Shoreline’s technology as well as its management. They go a long way toward ushering in what Xanthopoulos called “the era of cell therapy.”

Shoreline’s growing success is based on two pillars: solid science and experienced management.

“You have to have the high science, but also enormous institutional know how,” Xanthopoulos told BioSpace. “These cells are finicky. There are significant challenges in manipulating them. Our founders have 20 years’ experience in this field.

“BeiGene and Kite share our vision, and have extensive experience themselves – BeiGene is incredible in protein engineering and Kite pioneered CAR T therapies,” he said. So, when they chose to partner with Shoreline, they had performed competitive analysis and were saying, in essence, “we believe in you and your capabilities.”

These partnerships allow Shoreline to fast-forward its platforms.

“For a company to bring so much capital and synergy to work is incredibly powerful, unique, and differentiated,” Xanthopoulos said. “It is difficult to find another early-stage preclinical company that has this kind of recognition and validation.”

The new clinical data from Fate Therapeutics regarding its NK and T cell therapies help the field, too.

“The science is very comprehensive, and we believe it will bring those programs forward, renewing interest in pluripotent stem cells and NK cells,” Xanthopoulos surmised.

Shoreline Biosciences is developing off-the-shelf allogeneic therapies, bringing the benefit of stem cell therapies to many more patients than is possible with autologous transplants.

For autologous therapies, Xanthopoulos explains, “It is costly to take patient cells, manipulate them in the lab, add guided chimeric antigen receptors, and return them to the patients There also are issues with rejection, as well as the more significant issues of cytokine release syndrome. Patients with aggressive tumors don’t have the four to six weeks that method requires.”

Shoreline’s allogeneic approach, therefore, creates targeted, off-the-shelf stem cell therapies.

“The only effective way to do this is to start with pluripotent stem cells that can differentiate into more than 200 cell types,” Xanthopoulos said. “At Shoreline, we differentiate into hemopoietic cells. We are focused on NK cells and macrophages.”

“We have, basically, released the brakes for proliferating and activating the NK cells,” he said, by editing out a negative regulator of activation and proliferation to create what essentially is a supercharged cell that is more metabolically fitted.

Preclinical studies in animals show the cells resist exhaustion, conferring a better pharmacokinetic profile and the need for fewer cytokines. Importantly, those efforts have been validated by independent researchers, in many published papers.

Results indicate the combination of pluripotent stem cells and NK cells results in a greater ability to kill various tumor cells using 5- to 10-fold less IL2 and IL15. Consequently, Xanthopoulos said, “The overall therapy is less expensive.”

Shoreline Biosciences plans to take this program into early human trials in the second half of 2022.

“In 2023, we expect to file one or two Investigational New Drug (IND) applications,” he said.

The benefit of an allogeneic iPSC approach to therapeutics development is clear.

“You can perform a lot of genomic edits at the pluripotent state without a great many technical problems,” he noted.

For example, transducing macrophages with chimeric antigen receptors (CAR) requires specialized vectors and results in low yields. “But, if you start with pluripotent stem cells, you can make the modifications, isolate a single clone with the characteristics you want, and generate trillions of cells.” With one patient dose requiring approximately 100 million cells, this method can lower the approximate $400,000 cost of therapy substantially.

To do this for NK cells, Shoreline Biosciences created a unique, powerful engine and then determined how to decorate the resulting cells. After considering such issues as cell signaling, targeting, and toxicity, Xanthopoulos said, “We engineered what you can think of as hooks where antibodies recognize and interact tightly, for higher killing activity.”

As Xanthopoulos, a serial entrepreneur who has founded and operated four previous biotech companies, told BioSpace, “I’ve never been more excited. Stem cell therapies are proven. They are the next frontier of medicine.”

They aren’t in the distant future, either. “I think the era of cell therapies is here and now, and will dominate the landscape going forward. If we learn to make less immunogenic therapies, stem cell therapeutics will continue to increase momentum.”

As Shoreline looks to the future, it is building an expansive team and is continuing to hire in all categories. “We plan to double to about 100 employees in the next six to nine months, and have several outstanding investors onboard.”

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