Harnessing the body’s natural killers to target cancer

Nature Research Custom Media
Natural killer cells, the body’s first line of defence against emerging cancers, could be engineered into powerful, off-the-shelf cancer therapies.

Natural killer (NK) cells are part of the innate immune system, the body’s first line of defense against cancer. Credit: Alpha Tauri 3D Graphics/Shutterstock

Billions of highly trained killers are flowing through your fingers right now. They patrol your internal organs, guard the tissues under your skin against invaders, and wipe out virus-infected cells. They remain vigilant against cancer — recognising and destroying the early signs of tumours before they can gain a foothold.

These tiny terminators, called natural killer (NK) cells, are one of the body’s strongest defences against illness and disease — and yet the hundreds of billions of NK cells in our own bodies sometimes aren’t enough. Now researchers want to engineer NK cells as reinforcements, and store ranks of those reinforcement NK cells to be called up and deployed as needed (see ‘Engineering a tumor killer’). They want to make these engineered NK cells available to cancer patients and others as living drugs, without having to personalize them for each patient, as is the case with other cell therapies.

“We want to make cells that work like drugs,” says Dan Kaufman, a professor of regenerative medicine at the UC San Diego School of Medicine and co-founder and chief scientific officer of Shoreline Biosciences. “When you take a blood pressure medicine or a cholesterol medicine, everybody gets the same thing. You know the doses and it’s standardized. Using these engineered NK cells, we can do that. We can make hundreds, or potentially thousands, of doses of these NK cells all the same and use them as off-the-shelf therapies.”

Immunotherapy strategies

The idea builds on the success of so-called CAR-T cells, which are used as immunotherapies against several types of cancer. These cell-based therapies are based on a different immune component, called T cells. By collecting a patient’s T cells, engineering them to make them more potent, and then infusing them into the body, scientists can supercharge the cancer-fighting ability of the patient’s immune system. Five CAR-T cell therapies have been approved by the US Food and Drug Administration against several blood cancers.

NK cell immunotherapy has not yet reached that stage. “The natural killer cell approach in terms of cancer immunotherapy is newer, and rapidly gaining recognition,” says Hans-Gustaf Ljunggren, who works on cell therapies at the Karolinska Institute in Stockholm, Sweden. “There are numerous clinical trials going on with various natural killer cell-based products.”

Although there are clinical trials of NK cells in progress for multiple different blood cancers, nothing has been approved yet.1 “But it’s not unlikely that we will see such products within the coming five years,” Ljunggren says.

To help translate his own research on NK cells into commercial therapies, Kaufman co-founded Shoreline Biosciences. The company raised $43 million in financing earlier this year and entered into two partnerships with two immunotherapy companies, Kite Pharma and BeiGene, to develop novel cell therapies. The company recently concluded another round of financing that raised an additional $140 million.

One of the goals of NK cell therapies is to make them significantly cheaper than CAR-T cell treatments, Kaufman says. “It’s very expensive to take out the T-cells, engineer them and give them back to each individual patient. It costs roughly half a million dollars to make the cells for one patient.” The process also takes several weeks.

Innate fighters

NK cell therapies can be made more quickly and at lower cost because NK cells function in a different way. T cells are part of the adaptive immune system, the body’s second line of defence against both viral infections and cancer. They are primed to recognise specific foreign proteins on the surface of a patient’s own cells. Because T cells from one person recognize healthy cells from other people as foreign, only a patient’s own T cells can be used as a therapy — hence the need to remove and engineer them at such cost.

NK cells work in the frontline innate immune response, in which they patrol the body and attack any cells that are not recognised as part of the host tissue. This more indiscriminate approach means that NK cells therapies can be sourced elsewhere and more easily given as a standard treatment to many different patients.

“You can essentially establish banks of hopefully potent NK cells that could then be distributed globally to be used for treatment of cancers,” Ljunggren explains.

Because they do not need to be taken from a specific patient, Kaufman began developing NK cells for potential therapies from induced pluripotent stem (iPS) cells — skin or blood cells that have been reprogrammed back into an immature state that lets them develop into any other type of cell.

“Dan is one of the pioneers in the generation of the IPS derived NK cells,” Ljunggren says. “And now IPS NK cells have become a very interesting and relatively new aspect of cell therapies.”

Genetic manipulation

Besides being more universal, deriving the NK therapies from pluripotent stem cells brings another advantage. Manipulating the genome of the stem cells before they are converted to NK cells offers a reliable way to introduce genetic changes that could improve potential therapies.

When faced with attacking NK cells, cancer cell don’t sit idly by. “We know there are ways that the tumour cells can sort of evolve to avoid the immune system,” Kaufman says.

Kaufman’s group has countered by engineering NK cells into better cancer fighters. “We can engineer these NK cells to provide additional mechanisms or more activated cells that seem to be able to overcome those barriers.”

They have done this by knocking out a gene called CISH, which is involved in regulating cell-signalling molecules called cytokines. NK cells without the CISH gene are more sensitive to the cytokine IL-15, which leads to greater cell proliferation. As a result, the cells live longer inside the body and show enhanced anti-tumour activity.2

Trials ahead

Several challenges remain. Like CAR-T cells, NK cell therapies seem less effective against solid tumours. And because they are not based on host cells, the engineered NK cells can trigger an immune response, which tries to reject them. Researchers deal with that at present with doses of chemotherapy to suppress the host immune system. But Kaufman says they are also working on a new type of “stealth” NK cell that can evade host immunity.

“Can you also engineer these cells to avoid that immune response? That’s a challenge for later,” he says.

Shoreline has completed preclinical testing on a potential NK cell therapy for acute myeloid leukaemia. The company is now working on ways to manufacture the cells to the required clinical grade, and to test them for safety. That work is on track, Kaufman says, and trials will begin soon.

Explore the anticancer potential of engineered natural killer cells here.


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Intelligent Cells: Shoreline Builds Immunotherapy Platform, Pipeline with $140M Financing


CEO Kleanthis Xanthopoulos touts the San Diego biotech’s engineering prowess in developing iPSC-derived NK cells and macrophages against cancer

Shoreline Biosciences has developed induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells and macrophages that are optimized by applying gene editing to target specific genes with properties sought by the company. San Diego-based Shoreline says its “intelligently engineered” NK cells can target and kill tumors more effectively and efficiently.

Shoreline Biosciences has nearly doubled its total capital by completing a $140-million financing that will help it further build its platform and pipeline, focused on developing natural killer (NK) and macrophage cellular immunotherapies derived from induced pluripotent stem cells (iPSCs).

The financing also gives Shoreline capital toward creating potent and persistent NK cell-specific Chimeric Antigen Receptors (CARs) as well as switchable CAR-NK cell engagers and macrophage-specific CARs to treat blood cancers, solid tumors, and other disorders.

Shoreline has developed iPSC-derived NK cells and macrophages that are optimized by applying gene editing to target specific genes with properties sought by the company. Shoreline says its “intelligently engineered” NK cells can target and kill tumors more effectively and efficiently.

“It is natural to think that we can take advantage of the biology of natural killer cells, and if we can make them more persistent, arm them with specific target missiles that we call chimeric antigen receptors and direct them towards the site of the tumor cell, it will have an effect,” Kleanthis G. Xanthopoulos, PhD, Shoreline’s chairman and CEO, told GEN Edge.

Shoreline reasons it can produce NK cells faster, less expensively, and with potential for re-dosing compared with CAR T cell therapies. Despite their effectiveness fighting blood tumors, CAR-T therapies have shown significant side effects, notably cytokine release syndrome and graft versus host disease. And while T cells require activation before they can be sicced on cancer cells, being part of the adaptive immune system, NK cells do not since they are within the innate immune system.

“We found out that you can engineer the cells to be a better athlete, metabolically better fitted. They can persist longer. They can withstand the tumor micro-environment, which is a hostile environment typically for any cell therapy approaches,” he added. “Armed with these additional properties, we’re hoping that we can have a huge impact on the tumor cells.”

In NK cells, for example, Shoreline has removed the cytokine-inducible SH2 (CIS) protein encoded by the CISH protein coding gene and known to block the interleukin (IL)-2 and IL15 signaling that is critically important for activating cell proliferation.

“If we can intelligently remove that CIS protein, we see an NK cell that responds better to cytokines and at much lower concentrations, is metabolically more active, is a metabolically better fitted cell. It kills better because it produces many more different cytokines and it also withstands the tumor micro-environment better,” Xanthopoulos explained. “That’s the whole idea of intelligent-designed allogeneic cells.”

Looking beyond cancer

Shoreline has chosen to focus on cancer given the huge unmet medical need and the innate ability of NK cells to fight tumors. Long-term, however, the company envisions fighting cancer as well as chronic and infectious diseases through cell therapies based on macrophages.

“We know that there are chronic diseases that eventually can be addressed with macrophage cell therapies that have the innate ability to repair damaged tissue, and you can think of a number of diseases down the road that potentially macrophages can have the ability to do that,” Xanthopoulos said.

“What stands between our goals and moving non-oncology clinical programs forward is the need to understand better the so-called immunodepletion and conditioning of these patients, which we’re doing in the oncology setting, but you can’t necessarily consider doing that for chronic disease,” he added. “We can address that in in the future but the immediate focus is on oncology.”

Could Shoreline someday create cell therapies that combine NKs and macrophages?

“The short answer is yes, they indeed can complement each other,” Xanthopoulos replied. “Down the road we can potentially consider combining those two, but obviously we need to study them in the clinic individually and understand how they behave before we take that step.”

Shoreline’s core cell therapy platform is already designed to produce a homogenous population of optimized, fully functional immune cells. By cloning a select master iPSC-derived NK cell with its new optimized genetic signature, the company said, it can amplify that superior NK cell to create an unlimited number of homogenous quantities of the living cell therapy. The cells are then cryopreserved and stored, ready to treat any number of patients within hours.

“The clonal expansion capabilities of pluripotent stem cells give us the ability to do all the engineering we want at the pluripotent stem cell level, then select the clones or the clone that has the phenotype and the genotype that we are interested in,” Xanthopoulos said.

“From that clone, we can engineer trillions of cells. The process is relatively straightforward. It’s a clonal expansion of the clone that we have identified, and it gives us the ability to then create from a single run currently up to 500 doses, and it the yield will certainly increase as we optimize and we move into what we call smart manufacturing, which we plan to bring online in a couple of years from now.”

To satisfy its initial manufacturing need to get its candidates into the clinic for Phase I studies, Shoreline has partnered with UC San Diego’s Advanced Cell Therapy Laboratory (ACTL). The company says its partnership with ACTL allows it to bring in-house GMP grade iPSCs to bank and rapidly initiate preclinical development and IND-enabling studies. [Shoreline Biosciences]To satisfy its initial manufacturing need to get its candidates into the clinic for Phase I studies, Shoreline has partnered with UC San Diego’s (UCSD) Advanced Cell Therapy Laboratory (ACTL). The company says its partnership with ACTL allows it to bring in-house GMP grade iPSCs to bank and rapidly initiate preclinical development and IND-enabling studies.

$300M in capitalization

Shoreline said the financing, announced Tuesday, brings its total capitalization to more than $300 million. Roughly half of that capital consists of upfront cash that Shoreline received when it signed a pair of cell therapy collaborations in June with big-name partners Kite, a Gilead Company, and BeiGene—collaborations that could generate more than 10 times Shoreline’s current capitalization.

Kite is also partnering with oNKo-innate to develop NK cells. Numerous other companies have expanded into NK cell drug development; Artiva Biotherapeutics, for example, is building a pipeline of NK cell products that include antibody-dependent cellular cytotoxicity (ADCC) enhancers and targeted NK cells engineered to express proprietary CARs. Artiva, Catamaran Bio, Dragonfly Therapeutics, Fate Therapeutics, Kiadis, and Nkarta are among other companies focused on NK cell development.

“These transformative corporate partnerships with Kite and BeiGene have tripled the size of our aspirations and clinical trials,” and thus the number of treatment candidates in Shoreline’s pipeline, Xanthopoulos said. “As such, we are expanding our capabilities in manufacturing.” Shoreline is already building a “smart” manufacturing facility in San Diego designed to enable full automation. Xanthopoulos said the facility will enable the company to keep costs low. “We will announce in the near future some additional collaborations to secure additional manufacturing capabilities,” Xanthopoulos added.

Kite and Shoreline are partnering to develop novel allogeneic candidates for several blood cancers. The companies’ collaboration is initially focusing on CAR NK targets, with Kite having an option to expand the collaboration to include an iPSC CAR macrophage program for an undisclosed target.

“We already have constructs that we received from Kite. They’re now engineered in the backbone of our NK cells that have the CISH knockout. And we’re putting them together, and advancing with the aim to be in the clinic with the KITE collaborations programs in the next couple of years,” Xanthopoulos said.

Kite—which participated in Shoreline’s $43-million Series A round completed last April—selected Shoreline as its strategic partner for a strategic expansion into allogeneic iPSC therapies based around NK cells, in due to the expertise of the laboratory of Dan S. Kaufman, MD, PhD, a UCSD investigator and Shoreline co-founder, who serves as the company’s Chief Scientific Officer.

Last year, Kaufman and Xanthopoulos joined 30-year biotech veteran Steven Holtzman, the former CEO of Decibel Therapeutics, and William Sandborn, MD, in co-founding Shoreline to commercialize research and tech developed in the labs of Kaufman and Sandborn, who is Director of the Inflammatory Bowel Disease Center at UCSD and Shoreline’s Chief Medical Officer. Shoreline is also developing and commercializing additional technologies from Scripps Research’s Calibr division.

NK Cell Partnership

With BeiGene, Shoreline agreed to develop and commercialize NK-based cell therapeutics by combining its research and clinical development capabilities with Shoreline’s iPSC NK cell technology. BeiGene will retain worldwide development and commercialization rights for up to four targets—two solid tumors two blood tumors—with Shoreline holding an option to retain exclusive U.S. and Canadian rights for two of those four, as well as royalties.

BeiGene paid $45 million upfront to launch their collaboration, which could generate more than $1.3 billion for Shoreline in additional R&D funding, milestone payments, plus royalties. Shoreline is overseeing clinical manufacturing, while clinical development will be led by BeiGene globally.

“What we show in partnering with BeiGene is their amazing global clinical development and protein engineering capabilities as we plan to potentially combine our cells with antibodies, or so-called engagers that further enhance the activity of our NK cells,” Xanthopoulos said. “Those are core strategic capabilities—not just from the financial and validation perspective, but importantly from the clinical focus perspective—therefore amplifying Shoreline’s capabilities.”

BeiGene received an option to acquire an equity stake in a subsequent Shoreline financing—an option BeiGene exercised when it joined Kite as an investor in the $140-million financing. The round was led by Aly Bridge Group—whose founder, CEO and CIO Frank Yu joined Shoreline’s board in connection with the financing.

Yu stated that Ally Bridge Group, which focuses its investments on what it deems best-in-class cell therapy companies from oncology to autoimmune diseases, “expects Shoreline to be a new category leader.”

Other new investors in the $140-million round included Eventide Asset Management, Irving Investors, Kingdon, NS Investment, Piper Heartland Healthcare Capital, and Superstring. They were joined by previous investors including Boxer Capital, BVF Partners, Commodore Capital, Cormorant Asset Management, Janus Henderson Investors, Stork Capital, and Wedbush Healthcare Partners.

The latest financing will help Shoreline fund an ongoing expansion: The company plans to double its workforce, now close to 50 full-time equivalents, and anticipates moving in the second quarter of 2022 into a new 60,000-square-foot headquarters in San Diego.

Shoreline has mostly completed its executive suite with the appointment of Scott Forrest, PhD as Chief Business Officer; he was previously CFO of Autobahn Therapeutics. Further expansion will focus on R&D, clinical operations, and Chemistry, Manufacturing and Controls (CMC).


California Life Sciences awarded Kite Pharma, a Gilead company, and Shoreline Biosciences the 2021 Strategic Partnership of the Year Award

Shoreline Biosciences, Inc. is thrilled and honored to be recognized by the California Life Sciences (CLS) as the #Pantheon2021 award winner for the Strategic Partnership of the Year Award. Thank you, Kite Pharma, a Gilead company; we are incredibly grateful for your continued partnership as we develop safe, effective, and affordable iPSC-derived cell therapies. 

Developing Allogeneic Induced Pluripotent Stem Cell Based Therapies to Kill Cancer Cells with Kleanthis Xanthopoulos Shoreline Biosciences

Nov 4, 2021

Kleanthis Xanthopoulos is Co-Founder and CEO of Shoreline Biosciences. He talks about the Shoreline cell therapy platform that uses standardized manufacturing of allogeneic induced pluripotent stem cells to create an effective treatment to kill tumor cells with multiple advantages over autologous T-cell therapies.

Kleanthis explains, “We are focusing specifically on two different effector cells, Natural Killers and Macrophages, and we derive them from a platform which is induced pluripotent stem cells. This gives us the ability to really engineer the NK cells and Macrophages that we derive from iPSC, so they become allogeneic standardized, meaning they can be introduced to any patient and then are targeted and specific.”

“Initial clinical results are showing us that iPSC derived NK cells don’t appear to have the kind of side effects that you see with T-cells. So we are very, very excited about that. And we are seeing that there’s a different dimension in cell therapies that can be served very, very nicely through these allogeneic pluripotent stem cell based therapies.”

After the interview, Shoreline announced it has raised $140 million in its latest fundraising round.

#ShorelineBio #ShoreBiosciences #Oncology #Immunotherapy #NKCells #iPSC #Macrophages #SanDiego

Download the transcript here

Shoreline Biosciences – (iPSC)-Derived Allogeneic Natural Killer (NK) and Macrophage Products

Dr. Kleanthis Xanthopoulos, co-founder,  Chairman  and CEO of Shoreline Biosciences, discusses the development of genetically engineered induced pluripotent stem cell (iPSC)-derived allogeneic natural killer (NK) and macrophage products that are intelligently designed for greater  specificity, potency and persistence, overcoming the limitations of early cell therapies, for use in oncology and regenerative medicine. 

Kleanthis is a serial biotechnology entrepreneur with over two decades of experience in the biotechnology and pharmaceutical research industries as an executive, company founder, chief executive officer, investor and board member.

Dr. Xanthopoulos has founded five companies, introduced three life science companies to NASDAQ and financed and brokered numerous creative strategic alliance and partnership deals with large pharmaceutical partners.In addition to his role at Shoreline Biosciences, Dr. Xanthopoulos is the Chairman of Stork Capital Life Sciences which focuses on building and investing in innovative biotechnology companies. Dr. Xanthopoulos is a member of the board of directors of IRRAS AB, Connect Biopharma, (NASDAQ: CNTB), Zosano Pharma, Inc., (NASDAQ: ZSAN), and is the co-founder and a member of the board of directors of privately held Sente Inc.

Previously, he served on the boards of LDO sp.a. (Milan, Italy), Odyssey Therapeutics, Anadys Pharmaceuticals and Regulus Therapeutics.

Dr. Xanthopoulos participated in The Human Genome Project as a Section Head of the National Human Genome Research Institute from 1995 to 1997. Prior to this, he was an Associate Professor at the Karolinska Institute, Stockholm, Sweden. An Onassis Foundation scholar, Dr. Xanthopoulos received his B.Sc. in Biology with honors from Aristotle University of Thessaloniki, Greece, and received both his M.Sc. in Microbiology and Ph.D. in Molecular Biology from the University of Stockholm, Sweden.


San Diego biotech raises $140M in quest for ‘one-size-fits-all’ cancer treatments


San Diego biotech Shoreline Biosciences announced Tuesday that it has raised $140 million to fund a one-size-fits-all strategy that would use genetically modified immune cells to kill cancer cells.

That’s a popular goal these days. The Food and Drug Administration has approved a growing list of so-called CAR-T therapies, which take a patient’s own immune cells, equip them to recognize and attack a certain cancer, and reinfuse those modified cells back into the patient.

This approach has proven life-changing for some people, but it’s got drawbacks. In some cases, CAR-T therapy triggers overwhelming inflammation that can be debilitating — even deadly. And making tailored treatments is expensive and time-consuming, sometimes taking several weeks. That’s time the sickest patients don’t have.

To avoid these issues, Shoreline’s taking a different tack, developing “off-the-shelf” immune cell therapies that could work across patients. To do so, the company is coaxing stem cells to grow into two types of immune cells in the lab. These are natural killer cells, which target cancerous and infected cells, and macrophages, which clear out dead cells, alert other immune cells and regulate wound healing and tissue repair.

CAR-T therapies use T cells, which can trigger strong immune responses but will also attack healthy tissue if used in a different patient. That’s why CAR-T is currently a bespoke treatment.

Shoreline’s idea is to equip natural killer cells and macrophages with proteins they’ll need to recognize and fight against different cancer types, including leukemias and lymphomas. The company plans to eventually target some inflammatory diseases, too.

“We want to ultimately use cell therapy in a community setting exactly like the way you take a pill for any chronic disease,” said CEO Kleanthis Xanthopoulos.

The company, founded in the spring of 2020, has raised more than $300 million. The latest

Imagining the future of medicine and healthcare is one thing, evolving those ideas from science fiction to science reality is quite another. But that’s exactly what the Bristol Myers Squibb (BMS) Research & Development site in San Diego is…

“We have tons of money,” Xanthopoulos said. “If we cannot prove that we can do what our vision states, then we’re not worth, obviously, that investment.”

The company expects to begin clinical trials on at least one of its experimental treatments by the end of 2022 and hopes to have a steady stream of one to two drugs entering clinical trials each year that follows.

Shoreline struck deals in June with two other biotechs, Kite and BeiGene, to help turn its basic science into biomedical breakthroughs. The deal with California firm Kite, a Gilead subsidiary, has Shoreline conducting early-stage research on three blood cancer treatments for Kite, which will take over once the drugs are cleared to enter clinical trials. That deal could be worth $2.3 billion-plus royalties if all goes well.

The biotech is also working with China-based BeiGene on four cancer-immune cell therapies. Shoreline will have the option to retain the rights to develop and sell two of these products in the U.S. and Canada, and Xanthopoulos says the collaboration could bring the company up to $1.3 billion.

Shoreline has close ties with UC San Diego, and has licensed much of its technology from stem cell expert Dr. Dan Kaufman, UCSD’s director of cell therapy, who is one of the company’s co-founders, serves as chief scientific officer and sits on the firm’s board.

Other local companies are also developing off-the-shelf immune cell therapies against various cancers, including Fate Therapeutics, Poseida Therapeutics and Artiva Biotherapeutics.

Xanthopoulos says there’s plenty of space for everyone, likening this wide-open field to antibodies, which countless biotechs use in different ways for different diseases. The veteran biotech entrepreneur has been the founding CEO of four other San Diego life science firms: Regulus Therapeutics, Anadys Pharmaceuticals, Senté Labs and IRRAS. Regulus, Anadys and IRRAS all went public, with Roche later acquiring Anadys for $230 million.

Shoreline, headquarted in Sorrento Valley, has about 50 employees, though the company will double in size within the next year and has already signed a lease to expand its presence in the Sorrento area.



Fresh off Kite and BeiGene deals, Shoreline ups the ante with a hefty crossover

Editor: Max Gelman

Though it may seem like Shoreline Biosciences is rapidly gaining momentum with a flurry of deals — and, now, a new funding round — Kleanthis Xanthopoulos doesn’t feel he’s in a rush.

The biotech’s chief executive put the bow on a $140 million Series B on Tuesday, as Shoreline continues a streak of wheeling and dealing that’s seen it partner with Gilead’s Kite and BeiGene these last few months. And despite the new raise technically being a crossover round with Ally Bridge Group leading the way, Xanthopoulos is taking his time in prepping a public offering.

“It’s only smart for us to be ready for an IPO, but we have so much capital we can pick the right timing,” Xanthopoulos told Endpoints News. “Practically, we’re going to be ready to become a public company. When the time comes, we’ll be set, but it’s good to have that luxury.”

Driving all the interest are Shoreline’s off-the-shelf cancer therapies, including a particular focus on iPSC NK cells and macrophages for various tumors. Partnered with Dan Kaufman’s lab out of UC-San Diego, Shoreline has built a war chest of $300 million to advance such treatments, build out its manufacturing capabilities and sign its high-profile collaborations.

Manufacturing specifically has a special place in Shoreline’s plans, as Xanthopoulos eventually hopes the company will be able to create NK cell therapies that will be used in the community setting. It’s a pitch that’s driven significant investment toward the field as a whole, with companies like Artiva gaining backing from blue-chip investors and Merck.

But Shoreline’s focus on pluripotent stem cells — compared to Artiva’s donor cell approach — gives it a key differentiating factor, Xanthopoulos said. The two have very different manufacturing processes and the CEO believes iPSC NK cells will prove safer and more cost-effective in the long run.

“We incorporated AI, automation to completely rethink how we’re going to create the manufacturing,” he said. “We’ve recruited people from the electronic chip manufacturing industry to see how it worked there. A large portion of the raise is earmarked to build that facility.”

The company is now sitting on 10 pipeline programs largely aimed at a variety of hematological and solid tumors. Xanthopoulos said there are nine candidates involving NK cells, including two in house, three from the Kite partnership and four being co-developed with BeiGene. The last is Shoreline’s in-house macrophage program, which is slightly behind the rest, the CEO said.

Xanthopoulos likes to think of it as not just Shoreline’s pipeline, however, but the pipelines of three different companies coming together. Moving forward, Shoreline is getting ready to send its first IND for the lead in-house NK cell therapy by the end of 2022, with plans to submit “one or two” INDs every year after that, Xanthopoulos said.

And once that’s accomplished, maybe the IPO will come. But Xanthopoulos isn’t counting his cell therapies before they come home to roost.

“We want to see [our therapies] as broadly available as antibodies,” he said. “It should be that simple given how safe the NK cells have proven to be in the clinic.”