Gene editing has just started to fulfill its promise as a therapeutic modality. Further progress depends on making gene editing therapies more relevant to more patients. This was the theme of a recent talk by CRISPR pioneer and 2020 Nobel laureate Jennifer Doudna, PhD, at Harvard Medical School. In this talk, which was titled, “Rewriting the Future of Health Care with Genome Editing,” Doudna emphasized that gene editing therapies need better delivery methods.

One way to meet this need, she suggested, would be to expand delivery options from ex vivo approaches to in vivo approaches. With ex vivo treatments, it is necessary to remove and replace cells or suppress the immune system. With in vivo treatments, it is possible for treatments to be administered completely inside the patient’s body. Accordingly, in vivo treatments are more convenient for patients and healthcare providers alike—so convenient, in fact, that their administration is practical at healthcare facilities of all kinds, not just large urban academic hospitals.

As reported by Alvin Powell in the Harvard Gazette, Doudna offered the following observation:

“[Figuring out how] we can achieve in vivo genome editing … is the bottleneck in this field. Broadly speaking, what we need to be addressing is how these editors are going to get into target cells in the body. It’s a really interesting, really big challenge, and there are many people working on it.”

Among them are Harvard Medical School researchers at the Massachusetts Eye and Ear Hospital who recently led a successful proof-of-concept study for a gene editing therapy. In the Phase I/II BRILLIANCE trial (NCT03872479), 11 of 14 Leber congenital amaurosis patients who were treated with an in vivo CRISPR-Cas9-based therapy, Editas Medicine’s EDIT-101, showed measurable improvement on at least one key vision test. Six showed improvement on two or more vision outcomes.

But at prices exceeding $1 million, gene editing therapies have been administered to only 250 people. Institutions working to raise that number include the companies in this A-List, which highlights the top 10 public developers of gene editing therapies or of platforms enabling development of therapies that apply editing technologies. Some of the listed have had success with ex vivo therapies; others, such as Editas, report progress with in vivo therapies.

The companies have been ranked on a composite scale based on:

  •  Portfolio: Number of approved treatments and clinical programs. (Portfolio assessments considered how far the clinical programs had advanced).
  •  Cash position: Cash, cash equivalents, and marketable securities, as disclosed by the companies in regulatory filings and press releases.
  •  Market capitalization: Product of the share price and the number of outstanding shares.

When this A-List was prepared, information about 2023 revenues wasn’t available for all of the companies we considered for inclusion. Indeed, revenue figures were available for only about half of the companies that ultimately made the list. We report the revenue figures we obtained even though we didn’t rely on them to determine company rankings.

Just missing the list at No. 11 was metagenomics-driven gene editing toolbox developer Metagenomi (MGX). Metagenomi went public in February, raising $81.1 million in net proceeds, providing a cash runway to support two IND applications and two additional development candidate nominations. At deadline, none of Metagenomi’s 13 programs were in the clinic. But in April, Moderna terminated a 2-1/2-year collaboration of undisclosed value to co-develop Metagenomi’s gene editing technologies, including base editors and RNA-mediated integration systems, helping shrink a stock whose value has tumbled 47% from its 52-week high of $12.74 on February 15, to $6.80 on May 8.

1. CRISPR Therapeutics (CRSP)
CRISPR Therapeutics cemented its gene editing leadership last December when it and partner Vertex Pharmaceuticals received the FDA’s first approval for a CRISPR-based gene edited therapy, Casgevy (exagamglogene autotemcel or “exa-cel”), for sickle cell disease. The following month, the FDA approved Casgevy to treat transfusion-dependent β-thalassemia. Headquartered in Zug, Switzerland, CRISPR Therapeutics ranked second in 2023 revenue with $201.206 million (adding only $504,000 in Q1) but first in all other criteria, from clinical activity (five programs, two of which are in Phase I/II trials) to market cap ($4.468 billion) to cash position ($1.694 billion).

2. Beam Therapeutics (BEAM)
Beam Therapeutics said on May 7 that it expects to treat 45 patients in the expansion cohort of its BEACON Phase I/II trial assessing co-lead candidate BEAM-101 in severe sickle cell disease, after successfully completing sequential dosing and engraftment for the three-patient sentinel cohort. Beam expects to report data from “multiple” patients in the BEACON trial in the second half of this year. Based in Cambridge, MA, Beam led gene editing companies in 2023 revenue with $377.709 million (it added $7.41 million in Q1) and was second in cash position with $1.19 billion (dipping to $1.095 billion in Q1). Beam finished third in market cap with $1.872 billion, but seventh in clinical progress (two programs, both Phase I/II).

3. Intellia Therapeutics (NTLA)
Intellia Therapeutics is enrolling patients in its pivotal Phase III MAGNITUDE trial (NCT06128629) assessing in vivo CRISPR-based candidate NTLA-2001 (Intellia leads development, with partner Regeneron Pharmaceuticals) in amyloidogenic transthyretin (ATTR) amyloidosis with cardiomyopathy. The first patients were dosed in March. Intellia plans to launch by year’s end two other Phase III trials—one evaluating NTLA-2001 in hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN), the other investigating NTLA-2002 in hereditary angioedema. Cambridge, MA-based Intellia is second in both clinical progress (two programs, including Phase I/II and long-term studies for NTLA-2002) and market cap ($2.319 billion), and it is third in cash position ($1.012 billion, sinking 6% to $953.384 million in Q1). It finished ninth in 2023 revenue with $36.275 million (adding $28.935 million in Q1).

4. Editas Medicine (EDIT)
Editas Medicine said on May 8 that it completed enrollment of the adult cohort of the Phase I/II/III RUBY trial (NCT04853576) assessing renizgamglogene autogedtemcel (reni-cel, formerly EDIT-301) in sickle cell disease, with “substantive” clinical data to be released later this year. Reni-cel is also under study in transfusion-dependent β-thalassemia in the Phase I/II EdiTHAL trial (NCT05444894), with data also set for release later this year. Based in Cambridge, MA, Editas scored fourth in clinical progress (both reni-cel programs), fifth in revenue ($78.123 million), sixth in cash position ($427.135 million, sliding 12% to $376,776 in Q1), but eighth in market cap ($451.469 million).

5. Wave LifeSciences (WVE)
Wave Life Sciences said on May 9 that it expects to deliver proof-of-mechanism data later this year from its Phase Ib/IIa RestorAATion-2 (NCT06405633) trial now underway, part of a clinical program assessing WVE-006 as a first-/best-in-class treatment for α1-antitrypsin deficiency. WVE-006 is a GalNAc-conjugated, subcutaneously delivered RNA editing oligonucleotide for which GSK has an exclusive global license. Singapore-registered Wave, whose U.S. headquarters is in Cambridge, MA, is fourth in both 2023 revenue ($113.305 million, adding $12.538 million in Q1) and market cap ($735.749 million), but ninth in both cash position ($200.351 million, declining 10% to $180.922 million in Q1) and clinical progress (one editing program, two trials including Phase I RestorAATion-1 [NCT06186492] and two nonediting programs).

6. Caribou Biosciences (CRBU)
Caribou Biosciences expects by year’s end to launch its Phase I GALLOP trial assessing CRB-010 in lupus nephritis and extrarenal lupus, reflecting expanded clinical development for the allogeneic anti-CD19 chimeric antigen receptor T-cell therapy with a PD-1 knockout. CRB-010 has shown encouraging initial safety and efficacy in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Co-founded by CEO and president Rachel Haurwitz, PhD, and Nobel laureate Jennifer Doudna, PhD, Berkeley, CA-based Caribou tied for 5th in the clinic (three programs, all in Phase I), and placed 5th in cash position ($328.827 million), but finished 9th in market cap ($331.918 million) and 10th in revenue ($34.477 million).

7. Verve Therapeutics (VERV)
Verve Therapeutics in April voluntarily paused an early-stage clinical trial of VERVE-101—the first base editing treatment to reach the clinic—after one patient showed an elevated level of a liver enzyme and a low platelet count. Investors sent shares tumbling 35%, but analysts were far more forgiving. The setback came five months after Verve enthusiastically presented the first human proof-of-concept data for the in vivo base editing therapy. Boston-based Verve placed 8th in clinical progress (two programs, both Phase Ib) and just 11th in 2023 revenue ($11.758 million, adding $5.695 million in Q1) but is 4th in cash position ($623.95 million) and 6th in market cap ($546.615 million).

8. Poseida Therapeutics (PSTX)
Poseida Therapeutics promised investors a renewed focus on its genetic medicine portfolio, as well as advancements in its emerging platform technologies. Among these is its Cas-CLOVER high-fidelity nuclease for enabling clean site-specific gene editing. Poseida uses Cas-CLOVER in manufacturing its three clinical programs (all Phase I, tied for fifth). Two are partnered with Roche—P-BCMA-ALLO1 for relapsed/refractory multiple myeloma, and P-CD19CD20-ALLO1 for B-cell malignancies—and the other is wholly owned P-MUC1C-ALLO1 for multiple solid tumor indications. San Diego-based Poseida also ranks 6th in revenue ($64.703 million), 8th in cash position ($202.202 million), and 11th in market cap ($260.252 million).

9. Sangamo Therapeutics (SGMO)
Sangamo Therapeutics showcased its Modular Integrase (MINT) platform and other next-generation genome engineering capabilities at the recent American Society of Gene and Cell Therapy annual meeting and in a bioRxiv preprint (“Systematic Development of Reprogrammed Modular Integrases Enables Precise Genomic Integration of Large DNA Sequences”). MINT is a protein-guided genome editing method designed to integrate large sequences of DNA into the genome. A pioneer in zinc finger nuclease editing, Richmond, CA-based Sangamo is third in clinical progress with three programs, (including TX200, a gene edited cell therapy to prevent kidney transplant rejection, in Phase I/II) and third in revenue ($176.232 million, adding only $481,000 in Q1). It is 12th in market cap ($107.4 million) and 13th in cash position ($81.002 million, tumbling 33% to $54.417 million in Q1).

10. Prime Medicine (PRME)
Prime Medicine is preparing to launch the first human trials of a prime editing therapy after the FDA cleared the company’s IND application in April for its first clinical candidate. PM359, designed to target the p47phox variant of chronic granulomatous disease, consists of autologous hematopoietic stem cells modified ex vivo using prime editors designed to correct a high percentage of cells containing the disease-causing mutation. The FDA clearance sparked a 27% surge in Prime’s shares, lifting its market cap to fifth with $682.965 million. Based in Cambridge, MA, Prime ranks 10th in clinical progress (PM359’s Phase I/II trial) and 11th in cash position ($121.665 million).


Don’t forget to read GEN’s Top Five Privately Held Gene Editing Therapy Companies.

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