Abstract
The estate of Henrietta Lacks has sued Ultragenyx Pharmaceutical in a federal court, accusing the gene therapy developer of unjustly profiting from therapies based on cells taken from her without her knowledge or consent in 1951 and used to create a cell line.
In a complaint filed in the U.S. District Court for the District of Maryland, Baltimore Division, Lacks' estate is accusing Ultragenyx of unjust enrichment. The estate is requesting that it receive from the company all net profits generated from its orphan disease gene therapies based on the cells—whose name “HeLa” is derived from the first syllables of Henrietta Lacks' name.
Henrietta Lacks died of cervical cancer in 1951. Her cells were harvested by Johns Hopkins doctors during a cervical cancer surgery that was conducted without her consent. 1
Ultragenyx was accused in the complaint of developing and mass producing HeLa cells for commercial research and therapeutic use, with the cells forming the basis of the company's platform for producing gene therapies. The platform was initially called HeLa PLC, but trademarked last year under the name Pinnacle PLC.
In June, according to the Lacks estate's complaint, Ultragenyx opened a 20,329 square-meter manufacturing facility with complete end-to-end gene therapy capabilities in Bedford, MA, to further advance its large-scale commercialization of the platform. The facility enables Ultragenyx to develop and produce gene therapy treatments at a greater scale leveraging the platform, which is capable of 2,000 L commercial-scale manufacturing.
“Ultragenyx has strategically positioned AAV-based gene therapy as a central pillar within its business model. But its purported competitive advantage is the theft of Mrs. Lacks's cells,” the Lacks estate contended in its complaint. “Ultragenyx's answer to the challenge of how to grow AAV vectors is to commercialize for profit Mrs. Lacks's stolen cells to produce AAV vectors at a massive scale—and moreover, to be able to produce a range of different AAV vectors using the same production platform.” 2
Ultragenyx at deadline had not commented on the lawsuit, filed August 10. The case, 1:23-cv-02171-DLB, has been assigned to U.S. District Judge Deborah L. Boardman, who was nominated by President Joe Biden and confirmed by the U.S. Senate in 2021.
Ultragenyx is the second company sued by Lacks' estate over the use of Henrietta Lacks' cells. The estate had pursued a case against Thermo Fisher Scientific, which was dismissed August 1 after the company and estate agreed upon a settlement over profits the company earned after developing tools using Henrietta Lacks' biological materials. Terms of the settlement have not been disclosed.
ALEXION ACQUIRES PRECLINICAL PORTFOLIO FROM PFIZER FOR $1B
Alexion, AstraZeneca Rare Disease, has agreed to acquire and license from Pfizer a portfolio of preclinical gene therapy programs and enabling technologies for $1 billion, plus tiered royalties on sales.
The portfolio numbers a dozen preclinical programs, some of which are expected to enter the clinic within the next 2–3 years, Marc Dunoyer, CEO of Alexion, AstraZeneca Rare Disease, told analysts on AstraZeneca's quarterly conference call. 3
Through the transaction, Alexion will add to its holdings several novel adeno-associated virus (AAV) capsids, for use in gene therapies across several undisclosed therapeutic areas. The AAV capsids will add to Alexion and AstraZeneca's combined capabilities in genomic medicine, which Alexion recently expanded by acquiring LogicBio for $68 million in a deal completed in November 2022.
Alexion said it aims to develop new genetic therapies with improved safety and efficacy profiles using the assets acquired from Pfizer—and that it will seek to welcome staffers from Pfizer whose work forced on developing the portfolio.
“(The) announcement represents another major step forward in Alexion and AstraZeneca's ambition to be an industry leader in genomic medicine, which has potential to be transformative and even curative for patients with devastating diseases,” Dunoyer said in a statement. “We look forward to continuing our work to develop enhanced platforms and technologies with broad therapeutic application while integrating best-in-class expertise to accelerate promising therapeutics into the clinic.” 4
Alexion said it plans to close the transaction in the third quarter of this year, subject to the satisfaction of closing conditions.
REGENERON TO ACQUIRE DECIBEL FOR UP TO $213M
Regeneron Pharmaceuticals has agreed to acquire Decibel Therapeutics for up to ∼$213 million, in a deal designed to strengthen the buyer pipeline by accelerating and further resourcing gene therapy programs being developed for hearing loss.
Through a 6-year collaboration, Regeneron and Decibel are partnering on Decibel's sole clinical candidate DB-OTO, a cell-selective AAV dual vector gene therapy designed to provide durable restoration of hearing to people born with profound hearing loss due to mutation of the otoferlin gene. Decibel gained U.S. Food and Drug Administration (FDA) clearance last year for its Phase I/II CHORD™ trial (NCT05788536), a study that was recruiting patients at deadline and is estimated to enroll 22 patients.
In addition, Regeneron and Decibel are collaborating on two preclinical candidates: AAV.103, an AAV gene therapy designed to restore hearing to individuals with a GJB2 deficiency, the most common cause of congenital hearing loss; and AAV.104, designed to restore hearing to individuals with a deficiency of the structural protein stereocilin.
The companies first joined forces in 2017, through a collaboration of undisclosed value to “discover and develop new potential therapeutics to protect, repair, and restore hearing.” The collaboration was modified in 2020 with the removal of Atonal homolog 1 (ATOH1) as a target, and changes to terms and plans for the DB-OTO and AAV.103 programs.
Regeneron agreed to pay $109 million upfront for Decibel, and an additional up to $104 million tied to achieving contingent value rights (CVR) milestones. In addition to the $4 per deal price, the CVR could generate for shareholders an additional: $2 cash per share upon the fifth participant being administered with DB-OTO in a clinical trial on or before December 31, 2024; and $1.50 in cash per share upon either the first participant being dosed with DB-OTO in a registration-enabling trial, or DB-OTO being accepted for review of a Biologics License Application by the FDA, a Marketing Authorization Application by the European Medicines Agency (EMA) or U.K. Medicines and Healthcare Products Regulatory Agency; or an equivalent application in Germany, France, Italy, or Spain, whichever occurs first, on or before December 31, 2028.
“We believe that Decibel's assets and specialized team will further strengthen our genetic medicines portfolio, enabling Regeneron to accelerate the development of innovative genetic therapies and a rich pipeline of hearing loss treatments,” said George D. Yancopoulos, MD, PhD, board cochair, chief scientific officer, and president of Regeneron. 5
TAYSHA RAISES $150M IN PRIVATE PLACEMENT ROUND
Taysha Gene Therapies has entered into a private investment in public equity (PIPE) financing that is expected to raise gross proceeds of ∼$150 million for the company.
Taysha said it expected to use net proceeds from the PIPE, together with existing cash and cash equivalents, to extend its cash runway into the third quarter of 2025, to primarily support clinical development of TSHA-102 in Rett syndrome, fund program activities for TSHA-120 in giant axonal neuropathy, provide working capital, and address other general corporate purposes.
Through the PIPE, Taysha will sell 122,412,376 shares of its common stock at $0.90 per share, as well as prefunded warrants to purchase up to 44,250,978 shares of common stock at $0.899 per prefunded warrant. The PIPE had been expected to close by August 16, subject to customary closing conditions.
The prefunded warrants will only be exercisable upon stockholder approval of an increase in the authorized shares of Taysha's common stock, which Taysha said it will seek to obtain at an annual meeting of stockholders to be held by December 31.
Jefferies is the exclusive placement agent for the private placement.
The PIPE was led by a new investor, RA Capital Management, with participation from PBM Capital, RTW Investments, LP, Venrock Healthcare Capital Partners, TCGX, Acuta Capital Partners, Kynam Capital Management, Octagon Capital, Invus, GordonMD® Global Investments LP, B Group Capital, and an unnamed large institutional investor.
Taysha announced the PIPE on the same day it reported positive initial clinical data from the first patient dosed with TSHA-102 in the Phase I/II REVEAL trial (NCT05606614). That data showed TSHA-102 was well tolerated with no treatment-emergent serious adverse events as of a 6-week assessment. A 4-week post-treatment assessment showed improvement in key efficacy measures, including Clinical Global Impression–Improvement (CGI-I), Clinical Global Impression–Severity (CGI-S), and Rett Syndrome Behavior Questionnaire (RSBQ).
“We are pleased by the support from this prestigious group of new and existing investors, which we believe highlights the enthusiasm of the early clinical readout of the first patient treated in our REVEAL trial and reinforces the potential of gene therapy to transform the lives of patients suffering from devastating diseases,” said Sean P. Nolan, Taysha's chairman and CEO. “With this capital infusion, we believe we are well positioned to continue to execute across key program milestones.” 6
NEUROPHTH THERAPEUTICS COMPLETES ∼$95M SERIES C+ FINANCING
Neurophth Therapeutics, a Chinese-based developer of gene therapies for ophthalmic diseases, has completed a Series C+ financing of ∼$95 million, with the proceeds set to be directed toward advancing clinical trials for the company's core products, enhancing the firm's research-and-development capabilities, and expanding its pipeline.
Neurophth's leading candidate NR082 (rAAV2-ND4), a treatment of Leber's hereditary optic neuropathy (LHON) associated with mtND4 mutation (ND4-LHON), has been granted orphan drug designation by the FDA and the EMA. Earlier this year, NR082 became the first gene therapy drug to complete patient enrollment for a Phase III clinical trial in China. The company has also concluded enrolling the first patient for Phase I/II clinical trials of the therapy in the United States.
According to Neurophth, its second candidate NFS-02 is the only gene therapy in the world that targets ND1-LHON. NFS-02 is the subject of a global multicenter clinical trial after becoming the first Chinese gene therapy to receive both Investigational New Drug (IND) clearance for clinical trials from both the China National Medical Products Administration and the FDA.
“Since the beginning of this year, we've made substantial progress in the clinical trials of our products. We plan to keep focusing on developing gene therapies for ophthalmic patients worldwide,” said Professor Bin Li, founder, Neurophth's chairman and CEO. “With the support of our investors and our technological acumen, we're positioned to accelerate our clinical trials and R&D of new drugs, delivering gene therapies to patients more quickly.” 7
The Series C+ financing was coled by Yangtze River-CMB International Industry Fund, Wuhan Optical Valley Financial Holding Group, Wuhan Hi-Tech Holding Group, Hubei KTLC, and Guangzhou Jinkong Fund. Several investment firms also participated in the round, including CMG-SDIC Capital, Silicon Paradise Asset Management and Yangtze River Industry Fund.
After the conclusion of its angel round of funding in August 2018, Neurophth completed its Series A financing in early 2020, followed by Series B and C rounds, the latter taking place in 2021.
ADDIMMUNE TO MERGE WITH SPAC, CREATING $500M HIV DRUG DEVELOPER
American Gene Technologies (AGT) has agreed to merge with 10X Capital Venture Acquisition Corp. III (10X III), a special purpose acquisition company, to create a new public company called Addimmune that has committed itself to developing a gene therapy functional cure for HIV. To that end, Addimmune will trade shares under the ticker symbol HIV.
The proposed transaction represents a premoney enterprise value of $500 million for Addimmune, with the combined company eligible to earn an additional $300 million tied to achieving clinical and priced-based milestones. 10X III and AGT have entered into a nonbinding letter of intent with an affiliate of Cantor Fitzgerald, an underwriter of 10X III's initial public offering, for a $50 million committed equity facility.
The boards of directors of Addimmune and 10X III have unanimously approved the proposed merger. The transaction is expected to be completed in the first quarter of 2024, subject to regulatory approval, the approval of the proposed merger by 10X III's and Addimmune's shareholders, and the satisfaction or waiver of other customary closing conditions.
“We're excited about our collaboration with 10X. They bring a deep understanding of both the capital markets and the innovation that drives Addimmune. They will be a valuable partner to shepherd the combined company into the public market,” said Jeff Galvin, CEO of AGT, who will also serve as the CEO of Addimmune. 8
In June, Addimmune announced plans to separate from AGT, a developer of gene and cell therapies founded by Galvin in 2008. AGT began human clinical trials in 2020 for AGT103-T, a single-dose lentiviral-based autologous cell therapy candidate designed to deliver gene therapy-modified HIV-specific CD4 T cells to people with HIV. After initial positive results in clinical studies, AGT decided to create a separate company to focus on completing those trials and pursuing commercialization of a functional cure for HIV.
The combined company also plans to spin off the non-HIV assets into an entity that will retain the AGT name.
ASTELLAS INVESTS $50M IN POSEIDA THERAPEUTICS
Astellas Pharma has agreed to invest $50 million in gene and cell therapy developer Poseida Therapeutics, with the aim of advancing Poseida's commitment to redefining cancer cell therapy.
Poseida focuses on researching and developing cell and gene therapies for cancer and rare genetic diseases through its proprietary genetic editing platforms. In oncology, Poseida has a broad pipeline of allogeneic chimeric antigen receptor (CAR) T-cell therapy product candidates for both solid and liquid tumors—including P-MUC1C-ALLO1, an allogeneic CAR-T cell therapy that is in Phase I development for the treatment of multiple solid tumor indications.
Astellas' $50 million investment consist of $25 million to be spent acquiring 8,333,333 shares of Poseida's common stock—∼8.8% of its outstanding common stock—at $3 per share in a private placement; and a one-time $25 million payment for a right of exclusive negotiation and first refusal to license, P-MUC1C-ALLO1.
Poseida has granted Astellas a board observer seat, which includes the ability to attend Poseida's scientific advisory board meetings, and notice rights related to any potential change of control of Poseida.
By investing in Poseida, Astellas said, it is strengthening one of its areas of primary focus, namely immuno-oncology, by supporting development of next-generation immuno-oncology drugs using multifunctional platforms. Astellas' immuno-oncology portfolio includes oncolytic viruses, bispecific immune cell engagers, small molecules, and cell therapy platforms.
“We are excited to enter this strategic relationship with Astellas, a premier biopharmaceutical company that shares our long-term vision that cell and gene therapies represent an exciting growth area for the development of innovative medicines for improving patient care,” Poseida CEO Mark Gergen said. 9