Abstract
The abrupt resignation of Peter Marks, MD, PhD, as director of the U.S. Food and Drug Administration (FDA)’s Center for Biologics Evaluation and Research (CBER), has sparked concerns from industry leaders and trade organizations that the agency’s ability to review and regulate gene therapies and other biological products would be irreparably damaged as a result.
“This is very bad for biotech at FDA,” Eric Topol, MD, chair of the Department of Translational Medicine and the director and founder of Scripps Research Translational Institute in La Jolla, CA, posted on X. 1
“We are deeply concerned that the loss of experienced leadership at the FDA will erode scientific standards and broadly impact the development of new, transformative therapies to fight diseases for the American people,” the Biotechnology Innovation Organization (BIO) stated. 2
Marks oversaw the approval of 22 gene therapies as CBER director, a position he had held since 2016. Marks joined the FDA 4 years earlier as deputy director of CBER, which oversees reviews and regulation of biologics that include vaccines, blood products, and cellular and tissue-based therapies, in addition to gene therapies.
During the pandemic in 2020–21, Marks played a leading role in shepherding agency review of vaccines funded through Operation Warp Speed, the first Trump administration’s initiative to catalyze development and deployment of COVID-19 vaccines and drugs.
Those efforts won praise from leaders in the cell and gene therapy field for Marks, who spoke frequently about the need for regulatory reform to take full advantage of the safety, effectiveness, and programmability of new technologies, including CRISPR genome editing.
Marks tendered his resignation, effective April 5, in a two-page letter dated March 28 to then-acting FDA commissioner Sara Brenner, MD. In his letter, Marks sharply criticized the policies of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr., a severe critic of the COVID-19 vaccines whose office has begun eliminating some 10,000 jobs across the FDA and other HHS agencies and has begun to overhaul the regulation of vaccines and drugs.
“I was willing to work to address the Secretary’s concerns regarding vaccine safety and transparency… However, it has become clear that truth and transparency are not desired by the Secretary, but rather he wishes subservient confirmation of his misinformation and lies,” Marks wrote. “My hope is that during the coming years, the unprecedented assault on scientific truth that has adversely impacted public health in our nation comes to an end so that [Americans] can fully benefit from the breadth of advances in medical science.” 3
HHS responded to Marks’ departure by stating that if he “does not want to get behind restoring science to its golden standard and promoting radical transparency, then he has no place at FDA under the strong leadership of Secretary Kennedy.” 4
Succeeding Marks on an interim basis is Acting CBER Director Scott Steele, PhD, an FDA science, technology, and policy professional who previously served as senior advisor for translational science in CBER’s Office of Center Director.
ATSENA, ARBOR CLOSE COMBINED $223.9M IN SERIES C FINANCINGS
A pair of genetic therapy developers, Atsena Therapeutics and Arbor Biotechnologies, have completed a combined $223.9 million in Series C venture financings, reflecting investor confidence in the specialty at a time when startups in several other biotech specialties have struggled to raise capital.
Atsena, which aims to develop treatments that reverse or prevent blindness, successfully closed an oversubscribed $150 million Series C financing. Proceeds from the financing will be used to advance Atsena’s lead program, ATSN-201, for the treatment of X-linked retinoschisis (XLRS), as well as support Atsena’s preclinical pipeline of first-in-class therapies and expand the use of Atsena’s novel spreading AAV.SPR capsid, an application of adeno-associated virus (AAV) technology tailored to overcome the hurdles presented by inherited retinal diseases.
“Closing our Series C marks a pivotal moment for Atsena as we advance our transformative ocular gene therapies and fuel our next phase of growth, innovation, and clinical progress,” said Atsena CEO Patrick Ritschel. 5
He said the financing followed 12 months of achievements that included securing a partner to advance ATSN-101 to a global pivotal trial for Leber Congenital Amaurosis type 1 (LCA1) and launching Part B of the Phase I/II LIGHTHOUSE trial (NCT05878860), designed to assess the safety and tolerability of ATSN-201 in boys and men ages 6 years and older with XLRS associated with the RS1 gene.
Atsena’s financing was led by Bain Capital’s Life Sciences team, with participation from an additional new investor, Wellington Management. All Atsena’s existing investors also participated in the round, including Lightstone Ventures, Sofinnova Investments, Abingworth, Foundation Fighting Blindness, Hatteras Venture Partners, Osage University Partners, and the Manning Family Foundation.
In conjunction with Atsena’s financing, Norbert G. Riedel, PhD, executive chairman and former CEO of Aptinyx and chairman of Alcyone Therapeutics and Eton Pharmaceuticals, will join Atsena’s Board of Directors.
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 editing program for a rare liver disease and a program targeting amyotrophic lateral sclerosis.
“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],” said Devyn Smith, PhD, CEO of Arbor Biotechnologies. 6
Vertex Pharmaceuticals 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.
“Arbor is developing a differentiated portfolio with first-in-class potential to deliver on the promise of CRISPR-based genetic medicines,” said Keith Crandell, co-founder and partner at ARCH Venture Partners. 7
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.
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.
SPARK PLANS HUNDREDS OF PHILADELPHIA LAYOFFS
Spark Therapeutics plans to lay off nearly half of its Philadelphia workforce this year, following lower than anticipated sales of its marketed gene therapy Luxturna® (voretigene neparvovec-rzyl), a treatment for patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.
Spark has filed a notice with Pennsylvania officials under the Worker Adjustment and Retraining Notification (WARN) Act disclosing plans to eliminate 298 positions based at three Philadelphia locations in three waves: 124 will be laid off May 9, another 112 on July 1, and the remaining 62 workers by December 31.
However, a Spark spokesperson said that 337 employees will ultimately be laid off, while the remaining 310 Philadelphia-based employees will remain and be integrated into ongoing activities of Spark’s parent company, Roche Group. 8
The layoffs occur as Roche has begun restructuring Spark, a subsidiary focused on gene therapy, by integrating some of Spark’s activities within Roche’s Pharmaceutical Division while keeping other activities based at Spark’s Philadelphia site.
The restructuring follows a reassessment of Spark’s strategic future that began in the second half of 2024. The reassessment and onset of restructuring activities at Spark cost Roche CHF 162 million ($183 million) in 2024, the company stated in its Finance Report 2024, and the company estimated in January that it will spend CHF 300 million (about $339 million) this year for restructuring costs and other potential obligations and commitments deemed as reasonably identifiable.
Roche has reported CHF 18 million (about $20.5 million) in Luxturna sales during 2024, compared with about CHF 46 million (about $51 million) in 2023. Roche has completely written off Spark, recording a full impairment of CHF 2.122 billion ($2.397 billion) as goodwill from its $4.3 billion acquisition of Spark, completed in 2019.
WITH $68M SERIES B, EPICRISPR PLANS TO FUND TRIAL OF FSHD CANDIDATE
Epicrispr Biotechnologies has raised $68 million in the first close of its Series B financing, with the proceeds intended to support clinical development of the company’s lead development program, EPI-321, which is expected later this year to become the first epigenetic therapy to enter the clinic for a neuromuscular disease.
EPI-321 is a first-in-class, one-time disease-modifying therapy for facioscapulohumeral muscular dystrophy (FSHD) that is designed to silence aberrant expression of DUX4, a gene that is incorrectly activated in FSHD and leads to progressive muscle degeneration. Delivered systemically via a clinically validated AAV vector, EPI-321 has shown robust suppression of DUX4 expression and protection of muscle tissue in preclinical models, according to Epicrispr.
Epicrispr plans to launch a global Phase I/II clinical trial of EPI-321 that is planned to be conducted with Pacific Clinical Research Network, a clinical research center in New Zealand. The U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for EPI-321, while New Zealand regulator Medsafe recently approved a clinical trial application for the epigenetic therapy as well.
In addition to supporting Epicrispr’s upcoming clinical trial of EPI-321, proceeds from the financing are also intended to help the company advance its broader pipeline.
“We are developing a first-in-class, one-time epigenetic therapy that targets the genetic root cause of FSHD,” Epicrispr CEO Amber Salzman, PhD, said. “The Series B financing and regulatory clearance to begin our first-in-human trial mark a pivotal milestone as we become a clinical-stage company.” 9
During the trial, patients will be dosed one at a time in monthly intervals. “We’ll be doing muscle biopsies at baseline, and we’ll also be doing it at three months and then 12 months,” she explained. “What we hope to see between baseline and three months is that we did in fact methylate that hypomethylated region.” 10
Epicrispr will assess whether that methylation translates to suppressing DUX4 by looking at downstream markers of the gene. At the 6- and 12-month marks, the company will assess functional measures such as muscle strength and gait.
EPI-321 has received the FDA’s Fast Track, Rare Pediatric Disease, and Orphan Drug designations.
Ally Bridge Group led the Series B financing, with participation from SOLVE FSHD, the venture philanthropy organization whose founder and chair is Chip Wilson, founder of Lululemon Athletica and an FSHD patient, along with other undisclosed new and existing investors.
Concurrent with the funding, Epicrispr has expanded its Board of Directors with the addition of Andrew Lam, PharmD, managing director and head of Biotech Private Equity, Ally Bridge Group; Eric Crombez, MD, Chief Medical Officer of Ultragenyx; and Jennifer King, PhD, former SVP of Business Development at Intellia Therapeutics and an expert in rare diseases and strategic partnerships.
CRO/CDMO AMPLIFYBIO SHUTTERS OPERATIONS
AmplifyBio, a contract research organization (CRO) and contract development and manufacturing organization (CDMO) specializing in gene as well as cell therapies, shut down in April after four years in business.
The company, based in West Jefferson, OH, said its decision followed “months of tireless efforts by the AmplifyBio leadership team, investors, and other key stakeholders to explore and exhaust all investment and acquisition possibilities.” 11
“Like any startup, AmplifyBio’s growth strategy relied on meeting revenue targets and a supportive investor climate. At the time AmplifyBio launched, market conditions were favorable for early-phase drug development,” the company said in a statement posted on its website that has since been removed. “That market sector has experienced a significant shift over the last couple of years, leading to a scarcity of investor financing for early-stage biotech companies, which greatly impacted the ability to grow.” 12
That was not the case in 2021, when AmplifyBio was launched with $200 million from investors that included Battelle and Narya Capital, the tech-focused early-stage venture capital firm co-founded in 2020 by J.D. Vance, who went on to be elected U.S. Senator from Ohio and is now Vice President under President Donald J. Trump.
AmplifyBio grew in 2022 by acquiring a research-and-development facility in South San Francisco, CA, and other assets from PACT Pharma. AmplifyBio closed that site last December and shifted the site’s operations to its AmplifyBio Manufacturing Enablement Center (AMEC) in New Albany, OH, whose grand opening the company celebrated last year. AMEC was located 34 miles northeast of the company’s West Jefferson site.
NC OFFICIALS CANCEL NOVARTIS $1.5M TAX INCENTIVE AGREEMENT
A committee of North Carolina’s Department of Commerce has canceled an agreement with Novartis Gene Therapies that offered the company up to $1.5 million in tax incentives tied to achieving job creation benchmarks in the development of a multi-product gene therapy manufacturing facility in Durham County.
The state commerce department’s Economic Investment Committee voted April 9 to cancel the incentives agreement at the request of Novartis. The vote came six years after AveXis—which became Novartis Gene Therapies upon being acquired by Novartis AG in 2018—committed to creating 200 jobs as part of plans to create a $60 million gene therapy production facility.
The company had been paid $61,500 after meeting earlier job creation milestones and exceeded investment targets tied to the grant. But at the end of 2023, the company hadn’t hired any employees eligible to count toward its year-end job-creation goal.
“Although Novartis will remain fully operational at the project location, the company does not expect enough growth to meet the headcount commitments,” Novartis Gene Therapies Secretary Jamie Huertas, who is also general counsel and head of U.S. corporate and finance legal at parent company Novartis, told North Carolina commerce department officials. 13
State commerce officials also denied an annual payment planned as part of a separate active grant of $2.2 million to Novartis Gene Therapies, citing a failure to meet job creation requirements during 2023.
The company had planned to add 200 jobs as part of a separate $55 million investment in the facility. While Novartis exceeded its investment target, the company created 99 jobs rather than the 180 required to receive the 2023 payment.
Novartis said it still plans to meet all performance conditions of the active grant. Novartis finished 2024 with 308 employees that counted toward its economic incentive grants, the company told state officials.