Hemophilia B

Be Biopharma to use MaxCyte’s Flow Electroporation® technology and ExPERT™ platform within its Engineered B Cell Medicines programsROCKVILLE, Md., April 02, 2024 (GLOBE NEWSWIRE) -- MaxCyte, Inc., (Nasdaq: MXCT; LSE: MXCT), a leading, cell-engineering focused company providing enabling platform technologies to advance the discovery, development and commercialization of next-generation cell-based therapeutics and innovative bioprocessing applications and Be Biopharma (“Be Bio”), a company pioneering the development of Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with genetic diseases, cancer, and other serious conditions, today announced the signing of a strategic platform license (SPL) to support the development of Be Bio’s BCMs programs. Under the terms of the agreement, Be Bio obtains non-exclusive research, clinical and commercial rights to use MaxCyte’s Flow Electroporation® technology and ExPERT™ platform. In return, MaxCyte is entitled to receive annual licensing fees and program-related revenue. “We are thrilled to support Be Bio’s pioneering efforts in the creation of Engineered B Cell Medicines (BCMs),” said Maher Masoud, President and CEO of MaxCyte. “Our technology and expertise will empower them to unlock the potential of human B cells to address the unmet medical needs of patients with genetic diseases, cancer, and beyond. This new class of therapies could be transformative, and we are excited to be part of this journey.” MaxCyte’s ExPERT™ instrument portfolio is the next generation of leading, clinically-validated electroporation technology for complex and scalable cell engineering. By delivering high transfection efficiency, seamless scalability and enhanced functionality, the ExPERT™ platform delivers the high-end performance essential to enabling the next wave of biological and cellular therapeutics. Be Bio is MaxCyte’s 27th clinical/commercial partnership overall, each of which generates pre-commercial milestone revenue, the vast majority of which include sales-based payments. About MaxCyte At MaxCyte, we pursue cell engineering excellence to maximize the potential of cells to improve patients’ lives. We have spent more than 20 years honing our expertise by building best-in-class platforms, perfecting the art of the transfection workflow, and venturing beyond today’s processes to innovate tomorrow’s solutions. Our ExPERT™ platform, which is based on our Flow Electroporation® technology, has been designed to support the rapidly expanding cell therapy market and can be utilized across the continuum of the high-growth cell therapy sector, from discovery and development through commercialization of next-generation, cell-based medicines. The ExPERT family of products includes: four instruments, the ATx™, STx™, GTx™ and VLx ™; a portfolio of proprietary related processing assemblies or disposables; and software protocols, all supported by a robust worldwide intellectual property portfolio. By providing our partners with the right technology platform, as well as scientific, technical and regulatory support, we aim to guide them on their journey to transform human health. Learn more at maxcyte.com and follow us on X (formerly Twitter) and LinkedIn. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at be.bio and our LinkedIn page. MaxCyte Contacts: US IR AdviserGilmartin GroupDavid Deuchler, CFA+1 415-937-5400ir@maxcyte.com US Media RelationsSpectrum Seismic CollaborativeAnya Bolshem abolshem@spectrumscience.com +1 732-284-1751 Nominated Adviser and Joint Corporate BrokerPanmure GordonEmma Earl / Freddy CrossleyCorporate BrokingRupert Dearden+44 (0)20 7886 2500 UK IR AdviserICR ConsiliumMary-Jane ElliottChris Welsh+44 (0)203 709 5700maxcyte@consilium-comms.com Be Bio Contacts: Investor Relationsir@be.bio Media:media@be.bio

Pictured: 3D rendering of human cells and DNA/iStock/iStock, anusorn nakdee 2023 was a banner year for cell and gene therapy, with seven FDA approvals, according to the Alliance for Regenerative Medicine. And the pace doesn’t appear to be slowing at all as the second quarter of this year gets underway. The advocacy group is anticipating an even bigger year for the CGT space in 2024, with a potential 17 approvals in the U.S. and EU combined, according to ARM’s annual Cell & Gene State of the Industry Briefing in January. “It seems like the FDA is really pushing forward with accelerated approvals for cell and gene therapies, and that’s quite encouraging to see,” Jack Allen, a senior research analyst at Baird, told BioSpace. “These can be quite expensive products to develop, and if we’re able to leverage abbreviated pathways to get them to market rapidly, I think that can really reignite enthusiasm for the space.” Allen noted that cell and gene therapy is somewhat de-risked by the fact that, in many instances, these treatments involve introducing the genetic sequence for a native functional protein. “I think there will be some bumps in the road as it relates to pressing forward rapidly with the technology,” he said, but “it seems like the FDA has buy-in and is willing to ride through some of those bumps.” Here, we take a closer look at six of the more notable cell and gene therapies approved during the past year—two of them under the FDA’s accelerated approval pathway—and preview some of the decisions on the horizon. Cell Therapies BMS’s Breyanzi Chronic lymphocytic leukemia and small lymphocytic leukemia On March 14, the FDA approved Bristol Myers Squibb’s Breyanzi as the first CAR T cell therapy for relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia. In the pivotal TRANSCEND 004 trial, Breyanzi elicited a complete response—something that is “basically unheard of” in patients with relapsed/refractory CLL, according to Rosanna Ricafort, vice president and head of late development hematology and cell therapy at BMS—in 20% of recipients, with responses lasting more than 35 months. The Big Picture In November 2023, the FDA launched an investigation into the “serious risk” of secondary malignancies in patients treated with BCMA- or CD19-directed autologous CAR T cell therapies. This led to the addition of a boxed warning to all six commercial CAR-T therapies at the time, including BMS’s Breyanzi. But industry leaders and the FDA itself have been supportive of CAR-T’s risk/benefit profile. Breyanzi’s approval in two more indications, along with the recommendation of FDA advisers to move Abecma and J&J’s Carvykti into earlier lines of treatment for multiple myeloma, have cemented this tone. Iovance’s Amtagvi Melanoma In one of the year’s most anticipated decisions, the FDA in February greenlit the first one-time cell therapy for a solid tumor, Iovance Biotherapeutics’ Amtagvi for unresectable or metastatic melanoma, under the accelerated approval pathway. Iovance is currently conducting a confirmatory study to verify the therapy’s benefit. The Big Picture Amtagvi is the first tumor-infiltrating lymphocytes (TIL) therapy, a treatment modality some experts say has advantages over CAR-T. While CAR Ts recognize only a small number of proteins on the surface of tumor cells, TILs can identify tumor targets derived from intra- or extracellular tumor proteins, Sammy Farah, CEO of Turnstone Biologics, told BioSpace. As of February 2023, there were more than 75 TIL immunotherapies in preclinical or clinical studies for various indications. Gene Therapies Orchard Therapeutics’ Lenmeldy Metachromatic leukodystrophy Last month, the FDA approved Orchard Therapeutics’ Lenmeldy as the first gene therapy for metachromatic leukodystrophy (MLD), a rare, degenerative disease characterized by loss of motor and cognitive function and early death. MLD is caused by a deficiency in the arylsulfatase-A (ARSA) gene, leading to a buildup of fatty substances in the cells. Lenmeldy is a single-dose infusion made from a patient’s own hematopoietic stem cells, which have been genetically modified to include functional copies of the ARSA gene. The Big Picture Lenmeldy joins a growing list of gene therapy firsts in pediatric diseases, including Sarepta’s Elevidys for Duchenne muscular dystrophy and bluebird bio’s Skysona for cerebral adrenoleukodystrophy. It is also the first FDA-approved treatment for MLD patients, “who previously had no treatment options beyond supportive and end-of-life care,” Orchard CEO Bobby Gaspar said in a statement. Vertex and CRISPR Therapeutics’ Casgevy Sickle cell disease, beta thalassemia Possibly the most celebrated approval of 2023 went to Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy, which in December became the first-ever CRISPR-based gene editing therapy in the U.S., for sickle-cell disease (SCD). Just one month later, Casgevy was also approved for transfusion-dependent beta thalassemia, more than two months ahead of its PDUFA date. The Big Picture Casgevy’s SCD approval came just over a decade after the publication of the Nobel Prize-winning CRISPR-Cas9 technology—a timeline many industry experts have deemed faster than what would normally be expected of a new modality. But CRISPR is not without its risks. Researchers have cited cell toxicity and genomic instability as potential side effects, which could potentially trigger tumor development. Scientists are now working to improve on the technology with new modalities, including base editing and epigenetic editing. Bluebird bio’s Lyfgenia Sickle-cell disease While the historic nature of Casgevy’s approval won the day, bluebird bio’s Lyfgenia, a lentiviral gene therapy, also got the FDA’s nod for SCD on Dec. 8, 2023. Treatment with Lyfgenia led to the complete resolution of vaso-occlusive events 6 to 18 months after infusion, making it another promising option for patients. The Big Picture Allen said Lyfgenia may have a couple of advantages in the SCD market. “Both [therapies] are incredibly transformative in that they effectively eliminate sickle-cell disease–induced pain crises. Lyfgenia I think is quite interesting in that there’s a longer durability of data . . . and they also have some data in stroke patients, which I think is going to be differentiating in the commercial marketplaces” given the prevalence of stroke in SCD. Lyfgenia also has the upper hand over Casgevy in terms of developing the infrastructure needed to deliver treatment to patients. Sarepta’s Elevidys Duchenne muscular dystrophy In one of 2023’s more controversial decisions, the FDA approved Sarepta Therapeutics’ Elevidys as the first gene therapy for Duchenne muscular dystrophy (DMD). Elevidys missed the primary functional endpoint in a randomized trial but won accelerated approval based on data showing it increased the expression of the micro-dystrophin protein—a biomarker the agency determined is “reasonably likely to predict clinical benefit” in DMD patients 4 to 5 years of age. The FDA’s green light followed an adcomm meeting where its advisers narrowly recommended the gene therapy for approval. Then, just four months after the approval, Elevidys failed a confirmatory trial. The Big Picture Elevidys’ approval kicked off a wave of momentum in the DMD space. In October 2023, the FDA authorized Santhera Pharmaceuticals’ Agamree, and just last month, Italfarmaco won approval for Duvyzat, the first nonsteroidal drug approved to treat patients with all genetic variants of the disease. On the Horizon Rocket’s Kresladi Leukocyte adhesion deficiency-I Rocket Pharmaceuticals had expected a decision on its gene therapy Kresladi, in development for the rare disease leukocyte adhesion deficiency-I, in March, but the FDA pushed the date back to June 30, 2024 in order to allow for more review time. BMS’s Breyanzi Follicular lymphoma and mantle cell lymphoma It’s a big year for BMS’s Breyanzi, as the company is expecting the FDA to decide on the CAR T cell therapy as a treatment for patients with relapsed or refractory follicular lymphoma on May 23 and for those with relapsed or refractory mantle cell lymphoma who have been treated with a Bruton tyrosine kinase inhibitor therapy on May 31. Pfizer’s Beqvez Hemophilia B After winning approval in Canada in January, Pfizer’s adeno-associated virus-based gene therapy fidanacogene elaparvovec—marketed as Beqvez in Canada—has a PDUFA date in the second quarter of 2024. Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.

The year started well for the biotechnology industry. Steady dealmaking coupled with a rebound in initial public offerings helped lift investor confidence and, with it, drugmaker stocks.While that optimism has moderated somewhat since, a series of decisions by the Food and Drug Administration over the next three months could help the sector sustain its upturn. The agency may expand approvals for two cancer cell therapies and clear a third vaccine for respiratory syncytial virus. Sanofi and Regeneron await a decision on a lucrative new use for their top-selling Dupixent, while Geron could see decades of drug research finally pay off.Here are five FDA decisions to watch in the second quarter.CAR-T therapies for early multiple myeloma treatmentThe FDA this quarter could broaden the use of two cell therapies for multiple myeloma in decisions potentially worth billions of dollars to their respective developers.By April 5, the agency will decide whether to clear Johnson & Johnson and Legend Biotechs Carvykti for use in myeloma patients as early as after one relapse. That decision could be accompanied by a similar OK for Bristol Myers Squibbs Abecma and open up use of the therapies, which are currently only available in the U.S. for people with more advanced disease.European regulators have already endorsed earlier use of Abecma and Carvykti based on trial data showing they help people live longer without their disease progressing. But the FDA has appeared less supportive. The agency delayed a decision on Abecma last year and held a March advisory meeting to more closely scrutinize the data for it and Carvykti. In briefing documents, staff scientists flagged an apparent increase in the risk of death early on in the clinical trials of both therapies.The companies attributed that finding to limitations in the bridging therapies study participants could receive while waiting for CAR-T treatment. Panelists were convinced and backed both, agreeing that those issues likely wouldnt occur as frequently in practice.Nonetheless, the regulatory scrutiny suggests that the FDA might put new safety restrictions on Carvykti and Abecma if it chooses to clear them for earlier use. Jonathan GardnerModernas vaccine for RSVCOVID-19 vaccine makers Pfizer and Moderna have been facing the downside of their pandemic success, as falling sales have brought tough questions from investors.Moderna, for its part, aims to follow its COVID shot with several other messenger RNA-based vaccines, including one for respiratory syncytial virus thats now under FDA review.Respiratory syncytial virus, or RSV, can cause severe illnessin infants, older adults and people with compromised immune systems. Two vaccines, from GSK and Pfizer, are already approved to prevent RSV-related disease in adults over the age of 60. Sales of each have been strong, although GSK has established a clear edge.Moderna argues its vaccine, dubbed mRNA-1345, can compete. The shot is a pre-filled, single-dose vaccine, potentially offering more convenient administration.In Phase 3 testing, the vaccine was 84% effective at preventing infection with two or more symptoms in older adults. That efficacy does appear to wane over time, however.At a recent meeting, Centers for Disease Control and Prevention advisers reviewed known safety risks for GSKs and Pfizers shots, both of which were associated in very rare cases with Guillain-Barr syndrome, or GBS, a neurological condition affecting the nerves. Moderna has not reported any cases of GBS in Phase 3 testing of its shot.An FDA decision on mRNA-1345 is set for May 12. Delilah AlvaradoGerons imetelstat for myelodysplastic syndromesDrug development is a time-consuming, expensive process. Geron, a biotech founded 34 years ago to pursue stem cell research, knows this well.The companys long journey may finally reach an end by June 16, when the FDA will decide whether to approve a bone marrow disease drug Geron has been developing for nearly two decades. Called imetelstat, the drug treats myelodysplastic syndromes and some analysts believe it has blockbuster potential.Over the many years of Gerons research, imetelstat failed studies in multiple cancer types, and the company lost Johnson & Johnson as a partner along the way. But the drug finally succeeded in Phase 3 testing for myelodysplastic syndromes last year. And in March, it secured the endorsement of an FDA advisory panel despite skepticism from agency reviewers.Geron aims to challenge Bristol Myers Squibbs Reblozyl, first with a clearance in people with lower-risk disease and then in more people who have the condition. Stifel analyst Stephen Wiley estimated the drug could generate $2 billion in peak yearly sales, as it could be helpful in people who dont respond well to Reblozyl.Geron could be a buyout target, too, according to Wiley, though the company has said it plans to sell the drug on its own. Ben FidlerSanofi and Regenerons Dupixent for COPDDupixent is one of the pharmaceutical industrys most widely used and lucrative products. Approved for asthma, eczema and three other inflammatory conditions, the drug earned the companies more than $11 billion in sales last year.By June 27, the FDA could add another major indication to Dupixents list of approved uses. The regulator is currently reviewing the injectable medicine as a treatment for a type of chronic obstructive pulmonary disease, or COPD.If cleared by the FDA, Dupixent would be the first biologic drug for people with moderate-to-severe COPD who also have evidence of whats called Type 2 inflammation. A pair of late-stage studies, which enrolled nearly 1,900 people, showed Dupixent could cut the rate of COPD attacks by about one-third. Analysts therefore expect the FDA to issue an approval and forecast billions of dollars in additional yearly sales. Ned PagliaruloPfizers gene therapy for hemophilia BSome time during the second quarter, the FDA will decide whether to clear a gene therapy from Pfizer for hemophilia B, the less common form of the blood clotting disorder.Reaching this point has been a long time coming for Pfizer, which licensed the therapy from Spark Therapeutics a decade ago. In subsequent testing, treatmentlowered bleeding rates and reduced the need for regular blood transfusions powerful benefits meant to last many years with a single infusion.But its unclear whether Pfizer will find a market if the FDA chooses to approve its therapy. A rival genetic medicine, from CSL Behring and UniQure, won U.S. approval for hemophilia B in November 2022. However, few patients have been treated to date, sluggish uptake that could reflect the breadth of effective options available.The story is similar with Roctavian, a gene therapy BioMarin Pharmaceutical sells for the more common A form of hemophilia. Only three patients received Roctavian last year: two in Germany and one in the U.S.Pfizers therapy, which in January won Canadian approval, could provide another data point. But the company seems to be downplaying its potential. In recent presentations for investors, a once-weekly shot called marstacimab has gotten higher billing. Ned Pagliarulo '