A pair of privately-held developers of editing-based therapies have some successes to show for their recent efforts to address the longtime challenge of bringing their treatments to patients by sharpening their focus on specific therapeutic areas, with resulting cuts in their workforces, and doubling down on pipeline and platform development.
Gene editing therapy developer Arbor Biotechnologies completed a $73.9 million Series C financing whose proceeds are intended to support clinical development of its lead candidate ABO-101, a treatment for primary hyperoxaluria type 1 (PH1), and advance to clinical trials pipeline programs that include a reverse transcriptase (RT) editing program for a rare liver disease and a program targeting amyotrophic lateral sclerosis (ALS).
“The goal was to raise enough capital to get us into 2027, which allows us to have clinical data for the lead program, as well as have two additional programs having filed or close to filing their INDs [investigational new drug applications],” Devyn Smith, PhD, CEO of Arbor Biotechnologies, told GEN Edge.
Earlier this month Scribe Therapeutics, a developer of CRISPR and epigenome editing platforms and candidates based on its CRISPR X-Editor (XE) and Epigenetic Long-Term X-Repressor (ELXR) technologies, presented data showing that a single dose of ELXR using a newly identified repressor domain achieving ~90% repression of PCSK9, a key driver of dyslipidemia, lasting at least 150 days in nonhuman primates.
“Our latest data showcase the unmatched potency of our novel epigenetic editors, bringing safer, more effective therapies to patients with dyslipidemias and other cardiometabolic diseases. We believe this is more than an advancement—it’s a leap toward rewriting the future of medicine,” stated Benjamin L. Oakes, PhD, Scribe co-founder, president, and CEO.
Uphill climb
While that future is still expected to have a place for edited therapies, companies specializing in their development have faced a proverbial uphill climb in bringing those therapies through clinical trials and onto the market.
More than a year after Vertex Pharmaceuticals and CRISPR Therapeutics won FDA approval for the world’s first CRISPR edited therapy Casgevy® (“exa-cel” or exagamglogene autotemcel) for patients 12 years and older with sickle cell disease (SCD) or transfusion-dependent beta-thalassemia, the treatment has seen slower uptake among patients than expected by analysts.
Vertex reported just $10 million in 2024 revenue from Casgevy, most of which ($8 million) was generated in the fourth quarter. The Q4 revenue contrasts with the $14 million projected by a consensus of analysts, Jefferies analyst Maury Raycroft, PhD, reported in a research note.
Some blame the revenue figures on Casgevy’s list price of $2.2 million per course of treatment as a cost that insurers have balked at bearing, though Case Western Reserve University researchers noted in a 2024 review that SCD patients have many other treatment alternatives to Casgevy and Bluebird Bio’s even costlier ($3.1 million list price) gene therapy Lyfgenia
(lovotibeglogene autotemcel), such as stem cell or bone marrow transplants, as well as hydroxyurea. [Vertex and Bluebird cite patient access programs offering their treatments at below-list prices.]
At the end of 2024, Vertex said, it had activated more than 50 authorized treatment centers (ATCs) globally and more than 50 patients had initiated cell collection: “Vertex expects the number of new patients initiating cell collection to grow significantly throughout 2025,” the company said in announcing fourth quarter and full-year 2024 results.
Added Raycroft: “We expect the majority of 50 pts w/ cells collected to get [treated with Casgevy] in 1H25.”
Vertex is among previous investors in Arbor’s just-completed Series C as well as earlier rounds, though Arbor wholly owns its pipeline candidates, Smith said.
Joining Vertex were funds managed by abrdn (which is rebranding as Aberdeen), Ally Bridge Group, Arrowmark Partners, Deep Track Capital, Piper Heartland Healthcare Capital, Surveyor Capital (a Citadel company), Temasek, and T. Rowe Price Associates. They were joined by new investors QIA, Partners Investment, Revelation Partners, and Kerna Ventures. Leading the financing were ARCH Venture Partners and TCGX.
“Investors are looking for capital efficiency. They want people to be very efficient in the use of capital,” Smith replied. “You’re starting to see a lot more of that in the gene editing space where folks are starting to have more focused pipelines, which is a good thing.”
To enhance its efficiency, Arbor last September restructured its operations by cutting its headcount by about 20%. The reduction reflected the company’s pivot from developing its tech platform to developing therapies using that platform. Arbor was founded in 2016 by four co-founders including CRISPR pioneer Feng Zhang, PhD, a core institute member of the Broad Institute of MIT and Harvard.
“In the evolution of a company, particularly a platform company, you spend a lot of time and effort building the platform. We wanted to build a robust toolbox of gene editing approaches where you have a toolbox, you screen targets against that toolbox, you find the right approach. And at some point, you have enough tools in the toolbox that there’s no need to continue finding new tools,” Smith recalled. “We felt like we had hit that point last year, and that was the crux for making some of the changes we made. We felt the toolbox was pretty well mature, and it was time to focus on the pipeline and get that done.”
Arbor’s workforce now numbers about 100, a number that Smith said may increase one or two at a time, though the company may also lose one and two staffers incrementally as well.
“Have to evolve”
In January, Scribe also reduced its workforce, shedding about 20% of its headcount as it pivoted from tools to trials.
“This was really about starting to transition our focus toward development,” Oakes explained. “We’ve been operating as an organization focused on trying to build the best technologies and build them into assets for the past six years now. We have not yet developed a drug and that’s where we’re turning our eyes toward.”
Scribe’s headcount now stands at about 100. “We’re not in a growth stage right now,” Oakes said.
“I’m not saying it’s a foregone conclusion that every organization goes through this, but I think it is not unheard of to see organizations have to evolve as time goes on and they have to focus on different types or different aspects of drug development,” he added.
Scribe was founded in 2017 by co-founders that included Oakes and 2020 Nobel laureate Jennifer A. Doudna, PhD, a biochemist at UC Berkeley. Doudna is co-winner of the 2020 Nobel Prize in Chemistry, shared with Emmanuelle Charpentier, PhD, of the Max Planck Institute, for developing the CRISPR “genetic scissors” for gene editing.
Over the past couple of years, Scribe has focused its pipeline on treatments for cardiometabolic diseases. Scribe’s lead candidate is STX1150, an ELXR-based CasX-based epigenetic silencer being developed to treat elevated low-density lipoprotein cholesterol (LDL-C) by targeting PCSK9, now in the IND-enabling phase.
Last November at the American Heart Association (AHA) Scientific Sessions 2024, Scribe presented positive preclinical data showing STX1150 to have achieved durable methylation and suppression of the PCSK9 locus, resulting in sustained LDL-C reduction of up to 67% in non-human primates.
When is STX1150 expected to reach the clinic?
“It is not this year, but it is likely not far after that,” Oakes said. “Our timeline right now is next year, but we’re not providing many more details yet.”
At AHA, Scribe also presented data that it said validated both its XE and ELXR technologies in nonhuman primates. Scribe showed durable LDL-C reduction of up to 55% for at least a year through XE, in addition to the 67% lowering in ELXR-mediated LDL-C for nearly six months at therapeutically relevant doses. The XE technology also demonstrated reductions of apolipoprotein C-III (APOC3) protein by more than 90%, triglycerides by 97%, and total cholesterol by 84% in mice.
“Number one, cardiometabolic disease is the leading cause of morbidity and mortality globally. The standard of care is available widely, but very few people actually stay on it,” Oakes told GEN Edge.
Several studies have found that among patients with atherosclerotic cardiovascular disease (ASCVD), 50% or less receive statins and one-third or fewer achieve LDL-C goals below 70 mg/dL. “Despite the preponderance of evidence showing benefit of lowering LDL-C, utilization of lipid-lowering therapies and achievement of guideline-recommended LDL-C goals remain unacceptably inadequate,” a 2023 study concluded.
Bridging the gap
“We think there’s a huge gap in the technology that can really help us dramatically lower the number of heart attacks, and lower the number of deaths from cardiovascular disease. And we view our engineering approaches, which are critically focused on making more potent and dramatically safer genetic medicines, as being the solution to really bridge that gap,” Oakes said.
Also in Scribe’s pipeline are two lead optimization phase candidates based on its XE platform: STX1200, designed to treat elevated Lipoprotein(a) by targeting the LPA gene; and STX1400, an APOC3-targeting treatment being developed for severe hypertriglyceridemia (sHTG) and familial chylomicronemia syndrome (FCS). The company is also pursuing two discovery phase programs, each targeting a separate undisclosed cardiometabolic target.
“We are a very focused company, so we don’t have the bandwidth to do everything all at once,” Oakes said. “I would say we are really excited about STX1200 and STX1400, but they’re not moving forward at the same rate.”
Arbor’s pipeline is led by ABO-101, a one-time liver-directed gene editing treatment designed to treat PH1 by knocking out human HAO1 gene expression in the liver, thus providing durable reduction in oxalate production.
ABO-101 consists of a lipid nanoparticle (LNP) licensed from Acuitas Therapeutics, encapsulating messenger RNA (mRNA) expressing a novel Type V CRISPR Cas12i2 nuclease, as well as an optimized guide RNA that specifically targets HAO1. Cas12 nucleases are smaller than Cas9, allowing for easier transporting of genetic material.
Smith says the Cas12i2 nuclease it uses is wholly owned and developed by Arbor—not among the nuclease technologies and other gene editing assets the company inherited when it acquired another Zhang-founded startup, Serendipity Biosciences, last year for an undisclosed sum.
ABO-101 is being advanced through the Phase I/II RedePHine trial (NCT06839235), a multi-center, open-label, dose-escalation study designed to evaluate the drug’s safety, tolerability, pharmacokinetics, pharmacodynamics, and biomarker activity in PH1 patients. RedePHine is set to dose its first patient in the second quarter.
Up and running
“We’ve got clearance” of RedePHine’s IND application, Smith said. “And we are actively getting sites up and finding patients. So yes, the trial is up and running.” RedePHine’s estimated completion date is March 2029, according to ClinicalTrials.gov.
Another liver-focused Arbor candidate, ABO-103, applies an LNP and RT editing to target an undisclosed rare liver disease. ‘103 is in the discovery phase. Also in the pipeline are three candidates targeting ALS. The farthest advanced of these is ABO-202, an adeno-associated virus (AAV) vector designed to disrupt STMN2 using nuclease excision, now in the lead optimization phase. Also in lead optimization is ABO-204, an AAV that knocks down an undisclosed target. The third ALS candidate, ABO-203, is an AAV that uses nuclease excision against another undisclosed target.
Rounding out Arbor’s pipeline are collaborations in undisclosed phases and of undisclosed values with three biopharmas designed to apply ex vivo delivery to target numerous diseases. These include the development of an oncology-focused cell therapy with EdiGene; an autoimmune-focused cell therapy with Allogene Therapeutics; and treatments targeting type 1 diabetes, next-gen sickle cell disease (SCD), and beta-thalassemia among other diseases, all in a collaboration with Vertex offering up to $1.2 billion in milestone payments.
The Series C financing increases Arbor’s total capital raised to just over $300 million. The company emerged from stealth mode in 2018 with $15.6 million in Series A capital. Smith was appointed CEO in 2021, a few months before Arbor announced the completion of an oversubscribed $215 million Series B that funded the company’s pivot from toolmaking to therapeutics.
Arbor is among a handful of editing therapy developers to win financing this year. In January, epigenetic editing therapy developer Tune Therapeutics completed a $175 million Series B round intended to fund the development of the company’s pipeline, led by TUNE-401, a first-in-class treatment candidate for Hepatitis B (HBV) infection.
Scribe has raised about $120 million since it was established. While the most recent financing was the $100 million Series B raised in 2021, the company has also attracted investment capital from some of its collaboration partners.
Scribe’s partners include Eli Lilly-owned Prevail Therapeutics (an up to $1.5 billion neuro-focused collaboration launched in 2023—and Sanofi, from which Scribe in January received a milestone payment of undisclosed amount for one of two targets in its up-to-$1.2 billion-plus collaboration with Sanofi to develop in vivo CRISPR-based genetic medicines.
Does Scribe plan to pursue any additional financing?
I would say we are always looking for the right investors. I have no timeframe on that. That is just something we’re always looking for,” Oakes said. “We’re not looking for traders, but we’re always open to finding folks who align with our mission. We have been fortunate again to run a really tight ship in an area where many people have not done so, and I think that that gives us more flexibility to find the right people to work with.”
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