Cell & Gene Weekly

Gene therapy data in Hurler syndrome, new Astellas / Poseida pact, and more...

Many interesting news in the Cell & Gene world this week :) Enjoy the read and have a good weekend !

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Gene therapy for Hurler syndrome shows early signs of efficacy

A gene therapy from Orchard / Kyowa Kirin liscenced from San Raffaele-Telethon Institute for Gene Therapy has shown promising results in Hurler syndrome, a rare skeletal disease affecting children: the data for 8 patients was published in Science Translation medicine earlier this week, and to me seems pretty remarkable. At a median follow-up of 3.78 years after HSPC-GT patients exhibited:

• Longitudinal growth within WHO reference ranges

• Median height gain greater than that observed in patients treated with HSCT after 3-year follow-up

• Complete and earlier normalization of joint mobility compared with patients treated with HSCT

• Progressive decreases in mean AI and MP, suggesting a reduction in acetabular dysplasia

Overall, clinical, functional, and radiological measures suggest a meaningful beneficial effect vs allogeneic hematopoietic stem cell transplantation (albeit via indirect comparison) (!!!).

A picture is worth a thousand words: Check out below the graph with functional skeletal outcome (shoulder abduction) at baseline (left) vs after 3 yrs (right) - truly remarkable. Well done to the team at San Raffaele-Telethon Institute for Gene Therapy !! 👏👏

Source: Science Translational Medicine

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Astellas / Xyphos sign new pact with Poseida for “convertibleCAR” programs

Poseida will combine its allo CAR-T platform with Xyphos' ACCELTM technology to develop two candidates in solid tumors, dubbed the “convertibleCAR programs”. The underlying technology behind these programs, i.e., the “convertibleCAR” technology, is intended to create flexible cell therapies that can be engineered and re-engineered inside the body to target more than one tumor antigen, thus offering improved ways to mobilize immune cells to find and destroy target tumor cells. For the curious ones, more information can be found on the Xyphos website

This is not the first collaboration between Poseida and Astellas: last year they signed an agreement worth $50 M for the right to first refusal of a P-MUC1C-ALLO1 allo CAR-T for solid tumors. In this latest deal, Astellas will pay out $50 M upfront + possible $550 M biobucks and royalties on future sales.

P.S. The “convertibleCAR” program has a lot of hits on google - my favourite one below. Another CAR with a fun name that I like are the CAR-engineered TaNKs from Immunity bio :D

Source: fiercebiotech.com; xyphosinc.com

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Editas and BMS extended alpha-beta T cell tx collab 2026

The original collaboration dates back 2015 when then Juno Tx company signed an exclusive collab focused on creating CAR-T and high-affinity TCR tx for cancer. As you all know Juno was acquired by Celgene (for $9 bn !!), and Celgene by BMS: regardless, the collaboration has endured and has now been extended by further 2 yrs with options for further extensions into 2028. So far, BMS have already opted into 13 programs involving 11 gene targets, with two in IND-enabling studies and four in late-stage discovery.

Speaking of Juno, there’s a great article from Bruce Booth (Atlas Ventures) from a few years ago about how they passed on the opportunity to invest in Juno due to the complexity + unknowns around CAR-T and the lessons they learnt; my favourite passage below:

The loss of this opportunity reinforced another key lesson for us: if the data are truly transformational, you can work through all the other details later. It’s a very rare case when early data are truly this disruptive, but for those special situations you can’t let the small stuff (e.g., patents, licenses, people, etc) distract you from the big picture of having huge patient impact – just move forward and figure it out later. - Bruce Booth, Partner at Atlas Ventures [link]

Source: Investing.com; Forbes

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Quick take news

• Moderna exits Metagenomi gene editing deal worth $3B biobucks: Metagenomi will regain full development rights to its gene editing technologies that Moderna previously had rights to, such as its base editing and RNA-mediated integration systems (RIGS) [fiercebiotech.com]

• Precision BioSciences Announces Late-Breaking Poster Presentation at the European Association for Study of the Liver (EASL) Congress 2024 [Business Wire]

• NKGen Biotech Announces FDA Clearance of Investigational New Drug (IND) Application for SNK01 NK Cell Therapy in Parkinson’s Disease [yahoo finance]

• Latus Bio, developing novel gene therapy candidates for disorders of the central nervous system (CNS), raised $54M in Series A funding [finsmes]

• Prime Medicine Announces FDA Clearance of Investigational New Drug (IND) Application for PM359 for the Treatment of Chronic Granulomatous Disease (CGD) [Yahoo finance]

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Its earnings season - overall CAR-T sales flat QoQ, at just under the $1 bn mark

CAR-T sales from Gilead, Novartis, BMS and J&J are out: following multiple quarters of accelerated growth, we’re seeinng somewhat of a stall, perhaps capacity constrainsts?

Lets dig into the details:

• Flat revenue for Kymriah (now a recurring trend from the past ~2 yrs)

• Return to QoQ growth for Yescarta after what was a surprising drop in Q4 2023 attributed to “constraints within the existing ATCs” and “a little bit of in-class and out-of-class competition”

• Flat sales QoQ for J&J’s Carvykti, registering a 1% QoQ drop but a >100% increase vs Q1 2023.

• QoQ decline [-18%] for Abecma; seems like they are struggling to gain market share back from Carvykti, alongside increased out-of-class competition

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*Any views and opinions expressed herein are those of the author (Marco Sabatini) and do not necessarily reflect those of his employer