Next-Generation Therapeutics | October Roundup

Highlights & Summary

Intro

As we start the final quarter of 2022, there have been numerous exciting updates ranging from new company creation (Pheon Therapeutics) to major partnership moves forward (Pfizer & Voyager) and break-ups (GSK & AdaptImmune). We hope that this edition of our newsletter helps you navigate all the key developments that happened in October. 

Happy reading! 

Cell Therapy

1. Allogene moves its B-cell lymphoma CAR-T into a Phase 2 trial, as allogeneic therapies continue to make strides towards the clinic | Clinical Trial
2. Gilead looks to Refuge Biotechnologies’ platform for next-generation CAR-T | Licensing
3. Could an anti-mesothelin therapy finally succeed? TCR2 thinks so | Clinical Trial
4. GSK takes a step back on TCR-T candidates, handing back rights to its NY-ESO-1 candidate to Adaptimmune  | Partnership
5. Solid tumors, novel cell types, and allogeneic therapies all in one as NKGen gets IND clearance for a natural killer cell therapy | Regulatory

Gene Therapy

1. Lilly to acquire Akouos to gain portfolio of gene therapies for hearing loss | Acquisition
2. Astellas and Taysha Gene Therapies Announce Investment Supporting Taysha’s AAV-based Gene Therapy Programs | Investment
3. FDA accepts BioMarin’s BLA for valoctocogene roxaparvovec | Regulatory
4. Myrtelle partners with Forge Biologics for production of their AAV therapy for monogenic hearing loss | Partnership
5. Pfizer chooses to move forward capsid from Voyager Therapeutics | Partnership

Oligo Therapy

1. Ginko Bioworks Acquires Circularis to Strengthen Capabilities in Cell and Gene Therapy | Acquisition
2. NeuBase lays off 60% of employees as it swaps out antisense focus for gene editing tech endorsed by George Church | Pipeline
3. SiSaf to seek FDA Orphan Drug Designation for SIS-101-ADO | Rare Disease
4. Alnylam Announces FDA Approval of Supplemental New Drug Application for OXLUMO (lumasiran) in Advanced Primary Hyperoxaluria Type 1 | Clinical Approval 
5. Biogen Announces FDA’s 3-Month Extension of Review Period for the New Drug Application for Tofersen | FDA

Antibody-Drug Conjugates

1. miRecule enters into strategic collaboration with Sanofi to accelerate discovery and development of a best-in-class antibody-RNA conjugate to treat FSHD | Partnership
2. Avidity Biosciences announces Phase 1/2 EXPLORE44™ trial of AOC 1044 for Duchenne Muscular Dystrophy mutations amenable to Exon 44 skipping | Clinical Trial
3. Pheon Therapeutics launches with $68 Million in financing to advance novel Antibody-Drug Conjugates for treatment of solid tumors | Company Creation
4. Citing significant shift in the breast cancer competitive landscape, Ambrx Biopharma paused the internal development of ARX788 | Pipeline
5. U.S FDA accepts for priority review the sBLA for Gilead’s Trodelvy for pre-treated HR+/HER2- metastatic breast cancer | Regulatory

Cell Therapy

Allogene moves its B-cell lymphoma CAR-T into a Phase 2 trial, as allogeneic therapies continue to make strides towards the clinic | Clinical Trial

Allogene’s Phase 2, a potentially pivotal trial, is a step forward for allogeneic therapies. While this is definitely a beginning, there is a large number of allogeneic candidates in the clinic that we are tracking. 

Gilead looks to Refuge Biotechnologies’ platform for next-generation CAR-T | Licensing

It is clear that having a differentiated editing strategy is going to be a key driver in making the next generation of CAR therapies. It is also worth noting that Gilead specifically licensed the platform for blood cancers and not solid tumors.

Could an anti-mesothelin therapy finally succeed? TCR2 thinks so | Clinical Trial

There are a large number of failed anti-mesothelin cell therapies. So many that a good deal of players have given up on the target altogether. Even this early Phase 1 data for gavo-cel is an impressive achievement.

GSK takes a step back on TCR-T candidates, handing back to Adaptimmune the rights to its NY-ESO-1 candidate  | Partnership

This insight was originally revealed in a regulatory filing by Lyell, although Adaptimmune has since confirmed the news. This is going to be a big obstacle for Adaptimmune, and could signal GSK is bearish on the TCR-T space altogether.ad

Solid tumors, novel cell types, and allogeneic therapies all in one as NKGen gets IND clearance for a natural killer cell therapy | Regulatory

Another allogeneic NK cell candidate joins the fray as NKGen prepares to move SNK02 into the clinic. This candidate follows up on their autologous candidate (SNK01) already in the clinic.  

Gene Therapy

Lilly to acquire Akouos to gain portfolio of gene therapies for hearing loss | Acquisition

Lilly is signaling its increasing focus in gene therapies and hearing loss by acquiring Akouos. Akouos’ lead product candidate, AK-OTOF, is a gene therapy for the treatment of hearing loss due to mutations in the otoferlin gene (OTOF).

Astellas and Taysha Gene Therapies Announce Investment Supporting Taysha’s AAV-based Gene Therapy Programs | Investment

Astellas shows no slowing in appetite for AAV-based therapies. They just signed a partnership with Taysha that comes with an investment for an equity stake and potential future buy-out options. Taysha has recently had to cut back their pipeline and now focus on their therapies for Rett Syndrome and gant axonal neuropathy. 

FDA accepts BioMarin’s BLA for valoctocogene roxaparvovec | Regulatory

After BlueBird’s Zynteglo FDA approval, BioMarin’s BLA submission and FDA’s acceptance signals yet another gene therapy milestone targeting blood disorders. There is significant ongoing pipeline activity of gene therapies aiming at hemophilia A and B specifically, so this will certainly be an interesting space to watch in the near term. 

Myrtelle partners with Forge Biologics for production of their AAV therapy for monogenic hearing loss | Partnership

As Myrtelle’s novel gene therapy targeting autosomal recessive deafness (DFNB8), Myr-201, heads into clinical trials it has partnered with Forge to provide plasmid manufacturing and AAV process development. 

Pfizer chooses to move forward capsid from Voyager Therapeutics | Partnership

Pfizer has exercised its option to license Voyager’s novel capsid, developed from Voyager’s TRACERTM capsid discovery platform. The exercise of this option triggers a $10M payment to Voyager under the license agreement, which can see Voyager earn a further $580M in total future development, regulatory, and commercial milestones.

Oligo 

Ginko Bioworks Acquires Circularis to Leverage Proprietary RNA Platform | Acquisition

Ginko Bioworks has acquired Circularis. Circularis has developed a proprietary circular RNA and promoter screening platform. Ginko can leverage the Circularis platform in order to identify novel promoters across their cell and gene therapy programs. 

NeuBase prioritizes gene editing tech over antisense oligo programs | Pipeline

NeuBase is prioritizing gene editing technology and has deferred their pre-clinical ASO programs including myotonic dystrophy type 1 and Huntington’s. 

SiSaf Requested Orphan Drug Designation for its siRNA therapeutic SIS-101-ADO to treat skeletal muscle disorders | Rare Disease

SiSaf is seeking approval for SIS-101-ADO to treat Autosomal Dominant Osteopetrosis Type 2 (ADO2). This therapeutic combines an siRNA to suppress CLCN7 expression with their nanoparticle delivery platform. 

FDA Approves Alnylam’s OXLUMO (lumasiran) for Advanced Primary Hyperoxaluria Type 1 | Clinical Approval 

The FDA has approved a label expansion for OXLUMO for primary hyperoxaluria type 1 (PH1). The FDA approval is based on the ILLUMINATE-C Phase 3 study. 

Biogen Announces FDA’s 3-Month Review for Tofersen | FDA

The FDA has extended the review period for the new drug Tofersen, an antisense therapeutic targeting superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS). Tofersen binds to SOD1 mRNA, and reduces SOD1 protein expression. 

ADCs 

miRecule enters into strategic collaboration with Sanofi to accelerate discovery and development of a best-in-class antibody-RNA conjugate to treat FSHD | Partnership

Sanofi has entered an agreement with miRecule to develop and commercialize an antibody-RNA conjugate (ARC) for the treatment of FSHD. miRecule’s anti-DUX4 RNA therapy will be combined with Sanofi’s muscle-targeted NANOBODY technology. 

Avidity Biosciences announces Phase 1/2 EXPLORE44™ trial of AOC 1044 for Duchenne Muscular Dystrophy mutations amenable to Exon 44 skipping | Clinical Trial

AOC144 is the first antibody-oligonucleotide conjugate (AOC) to enter the clinic for the treatment of DMD. The lead asset targets exon 44 but the company has 2 additional programs for DMD, targeting exon 45 and exon 51.

Pheon Therapeutics launches with $68 Million in financing to advance novel Antibody-Drug Conjugates for treatment of solid tumors | Company Creation

Pheon Therapeutics plans to file an IND for its lead program within 1.5 years and forge ahead with establishing an extensive pipeline of novel ADCs for hard-to-treat cancers.

Citing significant shift in the breast cancer competitive landscape, Ambrx Biopharma paused the internal development of ARX788 | Pipeline

Ambrx Biopharma paused the internal development of ARX788 and will focus on strengthening existing partnerships while developing new ones to progress ARX788 ex-China.

U.S FDA accepts for priority review the sBLA for Gilead’s Trodelvy for pre-treated HR+/HER2- metastatic breast cancer | Regulatory

Gilead scored an FDA priority review for the expanded use of Trodelvy in metastatic breast cancer. The filing was based on data from the phase 3 TROPiCS-02 trial, and the FDA is aiming to take action within the next 6 months.