The first generation of cell therapies demonstrated how a patient’s own immune cells can be engineered into tumor-hunting cancer killers. Caribou Biosciences is among the biotech companies developing next-generation cell therapies that could offer manufacturing and therapeutic advantages over their predecessors.
Caribou’s story, and perhaps its pedigree (Jennifer Doudna, a Nobel prize winner for her CRISPR research, is a co-founder) captured strong investor interest that enabled the clinical-stage biotech to upsize its IPO. The Berkeley, California-based company initially planned to offer 17 million shares in the range of $14 and $16 each. Late Thursday, it boosted the deal’s size to 19 million shares offered at the top of the projected price range, raising $304 million. Caribou’s shares began trading on the Nasdaq Friday under the stock symbol “CRBU.”
A growing number of biotech companies are pursuing allogeneic cell therapies, “off-the-shelf” therapies that can be made in advance from donor cells, then stored until needed. These therapies could offer speed advantages, saving on the time required to manufacture a CAR-T therapy, which is produced by engineering a patient’s own T cells in a mostly manual process that can take weeks. But Caribou contends that genome editing technologies used in allogeneic cell therapy research have limitations when it comes to the multiple precise genomic edits that are needed to ensure the persistence of a cell’s therapeutic effect.
Caribou calls its technology chRDNA (pronounced chardonnay), which is short for CRISPR hybrid RNA-DNA. The company says that in preclinical research, this technology has demonstrated better specificity and efficiency, enabling multiple precise genomic edits with “significantly lower” levels of off-target edits. Caribou’s initial focus is developing allogeneic cell therapies that treat both blood cancers and solid tumors. The company is pursuing CD19 and B cell maturation antigen (BCMA), cell surface targets that have been validated by earlier cell therapies, as well as additional targets. But unlike the previous generation of cell therapies, Caribou says its cells could offer advantages.
“We use our chRDNA technology to enhance, or armor, our cell therapies by creating additional genomic edits to improve persistence of antitumor activity,” the company said in its prospectus.
Lead Caribou therapeutic candidate CB-010 is a CAR-T therapy that, like first generation CAR-T, targets the CD19 protein expressed on blood cancer cells. However, Caribou’s CAR-T is made by using the company’s technology to remove the PD-1 protein from the cell’s surface. The company said in the filing that knocking out this protein improves the persistence of the cell’s antitumor activity by disrupting a pathway that leads to rapid exhaustion of the T cell. CB-010 is currently being evaluated in a Phase 1 study that began at the end of 2020, enrolling patients with B cell non-Hodgkin lymphoma. Preliminary data are expected next year.
Caribou’s next product candidate, CB-011, is an allogeneic CAR-T cell therapy that targets the protein BCMA. The company uses its technology to incorporate an “immune cloaking approach” that removes one protein and inserts a transgene. Doing so is intended to blunt the rejection of the cell therapy by a patient’s T cells and natural killer cells, which in turn enables the cell therapy to have more durable activity against tumors. This program is in preclinical development for multiple myeloma. A filing seeking FDA permission to begin clinical trials is expected to be ready next year.
A third program, CB-012, is an allogeneic armored CAR-T cell therapy for acute myeloid leukemia that targets CD371. Caribou said that this protein is attractive target for AML because it is expressed on myeloid cancer cells but absent on hematopoietic stem cells. Caribou expects to file an investigational new drug application in 2023.
Since its founding in 2011, Caribou said it raised $150.1 million before the IPO. Its largest shareholder is President and CEO Rachel Haurwitz, with a 6.3% post-IPO stake, according to the prospectus. The largest institutional shareholder is F-Prime Capital, which owns 6.07% of the company after the IPO.
In February, Caribou began a partnership with AbbVie that paid the biotech $30 million up front. The alliance calls for the company to use its technology to develop two allogeneic CAR-T therapies. Caribou could earn up to $150 million in milestone payments for each program, plus up to $200 million in commercial milestones for each program. In the filing, Caribou said that it may seek additional collaborators.
As of June 30, Caribou reported having about $129.6 million in cash. That sum, combined with its IPO haul, will be deployed throughout the company’s pipeline. Caribou plans to spend $90 million for Phase 1 testing of CB-010 through the reporting of initial data, according to the filing. Another $80 million is set aside for the preclinical research supporting investigational new drug applications and the potential start of clinical testing of CB-011 and CB-012. The company plans to spend about $55 million on research and development of its platform for making natural killer cells from induced pluripotent stem cells, as well as discovery-stage research that could spawn additional programs.
Sophia Genetics’ IPO scores $234M for SaaS health data platform
Sophia Genetics raised $234 million by pricing its offering of 13 million shares at $18 apiece, right at the midpoint of its targeted price range. On top of the IPO cash, Switzerland-based Sophia is adding $20 million from GE Precision Healthcare affiliate Instrumentarium Holdings, which has agreed to purchase shares in the newly public company at the IPO price. Sophia’s shares will trade on the Nasdaq under the stock symbol “SOPH.”
Sophia’s software-as-a-service platform analyzes digital health data. The company says its technology enables healthcare institutions to obtain insights from their data.
“We envision a future in which all clinical diagnostic test data is channeled through a decentralized analytics platform that will provide insights powered by large real-world data sets and AI,” the company said in its prospectus. “We believe that a decentralized platform is the most powerful and effective solution to create the largest network, leverage data and bring the benefits of data-driven medicine to customers and patients globally.”
So far, Sophia’s products are available in the U.S. for research use only and therefore cannot be used for diagnosing or treating disease. In the future, the company plans to seek in vitro diagnostic status or FDA approval for specific uses of its technology. In Europe, Sophia’s products are self-certified. The European Union permits companies to self-certify in vitro diagnostic products, which means that no third-party needs to intervene to affirm that the product meets European health, safety, and environmental protection standards.
The first application of the Sophia platform, launched in 2014, analyzes next-generation sequencing data for cancer diagnoses. As of the end of June, the company counted about 330 applications used by healthcare providers, clinical and research laboratories, and biopharma companies. Those entities are using the technology for insights into disease areas including oncology, rare diseases, infectious diseases, cardiology, neurology, and metabolism.
In addition to clinical customers, Sophia has customers in the biopharmaceutical sector. These companies use the for work in the drug discovery, clinical testing, and commercialization stages. The biopharma applications launched in 2019.
The average annual revenue that Sophia generates from each customer is just over $70,000. In 2020, the company reported total revenue of $28.4 million, an 11.9% increase over the prior year. Sophia’s net loss in 2020 was $39.3 million. According to the prospectus, the IPO proceeds will be used as working capital and for other corporate purposes, such as R&D, selling and marketing, supporting relationships with collaborators and customers in healthcare, and obtaining regulatory clearance or approvals.
AI-powered protein production platform spurs Absci to a $200M IPO
Absci doesn’t have a pipeline of drugs that it plans to submit for FDA review. It doesn’t conduct clinical trials or even preclinical research. The company’s technology generates biologic drug candidates and production cell lines, all from a technology that it calls an AI-powered, integrated drug creation platform. Biopharmaceutical companies sign on as partners to use this platform. Absci stands to earn milestone payments as these drugs progress in development and royalties from sales if they reach the market.
With ambitions to expand its technology and sign on more partners that will use it, Absci raised $200 million from its IPO. The Vancouver, Washington-based company offered 12.5 million shares priced at $16 apiece, which was the midpoint of its projected price range. Those shares are trading on the Nasdaq under the stock symbol “ABSI.”
The biologic drug candidates that Absci develops stem from a technology founder and CEO Sean McClain describes as a marriage of artificial intelligence and synthetic biology. The platform produces proteins made by E. coli, the company explains in its IPO filing. These bacteria that have been harnessed before to manufacture insulin. Absci goes further, engineering E. coli to make complex mammalian proteins that can be the basis of new therapeutic candidates. The company says its technology enables it to do this work faster and more efficiently.
“We believe we can expand biologic possibilities, generate entirely new types of protein-based drugs, and give the best potential drug designs the opportunity to become therapeutic realities for patients,” McClain said in a letter included in the prospectus. “We believe that by marrying cutting-edge artificial intelligence with synthetic biology, we are stepping beyond the constraints of nature’s evolutionary trajectory, opening up a new sequence space for potential proteins, and even adding new letters to the amino acid alphabet to realize new possibilities for drug discovery.”
Currently, Absci has nine active clinical or preclinical programs in the hands of seven partners. The disclosed partners are Merck, Astellas subsidiary Xyphos Biotechnology, Alpha Cancer Technologies. As of the end of June, Absci reported a cash position of $99.5 million. Combined with the IPO proceeds, the company plans to further invest in and expand its technology and continue pursuing more business opportunities, the company said in its prospectus. Absci also said it may use some of its cash for acquisitions, though it added that there are no such deals currently in place.
Cytek Bio’s IPO raises $200M for cell analysis instruments
Cytek Biosciences, a company that sells cell analysis tools used in research applications, raised about $200 million in its stock market debut. The Fremont, California-based company priced more than 16.7 million shares at $17 apiece, which was the midpoint of its projected price range. About 11.7 million shares were offered by Cytek; stockholders in the company sold nearly 2.8 million shares. Cytek’s shares will trade on the Nasdaq under the stock symbol “CTKB.”
Cytek counts more than 620 customers around the world, the company said in its IPO filing. Its customer base is nearly evenly split between customers in academia and government, and industry customers comprised of companies in biotech, pharma, distributors, and contract research organizations. Cytek reported $92.8 million in revenue in 2020, a 60.3% increase over the prior year.
According to the prospectus, Cytek plans to spend between $112 million and $135 million on manufacturing, and between $44 million and $53 million on commercial activities and marketing.
Caribou photo by Flickr user Thomas via a Creative Commons license
