Top 10 Events in Cell & Gene Therapy 2022

2022 has seen some interesting developments in cell and gene therapy, with 254 new clinical trials announced with 202 at Phase III. However, investment is down across the field by 41% and the workforce has experience a record number of layoffs as companies look to restructure.

Susan kicked off the session by commenting on the “we are relentless as a community in staying on course to make sure we delivery these life-saving therapies.”

The session kicked off with a quick review of the top 10 events from 2021, which included:

• CAR-T Advances in Line of Treatment
• Investor Focus Expands to Tools and Technologies
• AAV Adverse Events
• Workforce Development Opportunities
• Expansion of CGTx-Focused End-to-End Service Providers
• Market/Patient Access
• In Vivo Gene Editing Enters the Clinic
• Advances in mRNA-Based Medicines
• Gene Editing Platforms Land Significant Investment
• Autologous CAR-T Process Improvements

But how do these compare to the top 10 list this year? Here’s a quick rundown as presented by Susan Nichols.

10 – Big Pharma Expands Toolkit

• Takeda $2B biobucks deal with Code Therapeutics to bypass AAV roadblocks on the way to gene therapy 2.0 for non-viral gene therapies
• Novartis $1.5B deal Precision ARCUS gene editing platform with $75M upfront for up to an additional $1.4B in milestones and tiered royalties on sales of licensed products
• Novartis and Voyager Therapeutics AAV virus capsid technology with potential for a 1.7b biobucks pact and $54m upfront
• Intellia- first in human gene editing biotech will receive $920m from ONK Therapeutics in a collaboration agreement focused on CRISPR- edited NK therapeutics

9 – First Gene Therapy Approval Beyond Rare Disease

• Ferring Pharmaceuticals AAV gene therapy, Adstiladrin, for the treatment of adults with high-risk Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer with carcinoma in situ (CIS) with or without papillary tumors
• One injection 51% of patients achieved a complete response

“This approval provides healthcare professionals with an innovative treatment option for patients with high-risk non-muscle invasive bladder cancer that is unresponsive to BCG therapy,” said Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research. “Today’s action addresses an area of critical need. The FDA remains committed to facilitating the development and approval of safe and effective cancer treatments.”

8 – Alternative Funding

• Priority Review Vouchers – bluebird bio sold to Argenx, a Netherlands based biotech, for $102m
• Bridge Bio Pharma sells rare pediatric disease priority review voucher for $110 million and defers principal payment on senior debt by 2 years
• Applied Genetic Technologies Corp sold to Syncona investment fund for a $23.5m
• Autolus sold $150 million worth of its stock immediately after pivotal data readout for obe-cel, as part of a previously filed shelf registration and looking to file a BLA 2023
• Autolus is also collecting $70 million in milestone payments from Blackstone per a $250 million collaboration and financing deal they struck late last year

7 – Hemophilia A and B Drug Approvals

• The European Medicine Agency approved a gene therapy for hemophilia A by BioMarin Pharmaceutical, Roctavian. Cost approximately €5m
  • After rejecting their first application, the FDA is now considering BioMarin’s resubmission
  • 33,000 patients total, with a breakdown of 75% Hemophilia A and 25% Hemophilia B
  • FDA rejected BLA in 2021 and accepted BLA this year
• FDA approved Hemophilia B, CSL Behring’s Hemgenix one-time treatment
  • Clear value for therapy with price tag of $3.5m with average patient consuming up to $20m of healthcare in their lifetime
  • Institute for Clinical and Economic Review (ICER) validated benefit of $2.5 m

6 – Big Pharma Dominates M&A

• Acquisitions
  • Eli Lily acquired Akous gene therapy for hearing loss $600m
  • Astra Zeneca $320m for Neogene cell therapy 2.0
  • Vertex $320m buyout of ViaCyte for islet cell space
  • Ultragenyx acquires GeneTX Biotherapeutics for $75m post partnership
• Mergers
  • Carisma and Sesen Bio merge under Carisma giving them a combined $180m cash to fund through 2024
• Partnerships/Collaboration
  • Collaboration between Roche and Poseida – $110m upfront, up to $110m in biobucks for hematologic CAR-Ts
  • Astellas acquired $50m Taysha stock for 2 CNS assets

5 – Larger Patient Population Growing Pains

On February 28, the FDA approved ciltacabtagene autoleucel (Carvykti) for adults with multiple myeloma that is not responding to treatment (refractory) or has returned after treatment (relapsed)

• Incredible data – 98% ORR and 78% complete response rate Mabs corresponding numbers J&J Tecvayli 62% and 31%
• Available only in limited number of hospitals while Janssen scales up production of Janssen and Legend bio asset
• One-month production time and wait list from day one

On March 26, the Food and Drug Administration (FDA) approved idecabtagene vicleucel (Abecma) by Bristol Meyers Squibb (BMS) for people with multiple myeloma that has not responded to or has returned after at least four different prior cancer treatments.

4 – Leveraging Trailblazers Prior Experience and Scale

• Big Pharma Manufacturing for Partner
• Gilead/Kite- Experienced Manufacturing with Yescarta and Tecartus
• Tmunity Acquisition for toolbox
• Kite will be responsible for manufacturing
• $225 million and cash and made a $100 million equity investment in Arcellx for 50% share CART-ddBCMA, a candidate treatment for patients with relapsed or refractory multiple myeloma.

Pharma Third- Party Manufacturing

• Novartis manufactures Carisma Car M program

Pharma Companies Establish Hubs

• Bayer $200 m investment in cell and gene facility in Berkeley CA
• Astellas South San Francisco CA hub $70 m investment

3 – First Allogeneic T-Cell Approval

• The first regulatory approval of an allogeneic cell therapy goes to Atara Biotherapeutics approved in the EU in December of 2022
• Ebvallo is the first immunotherapy off-the-shelf sourced from healthy donors to receive approval
• Ebvallo will be commercialized by French partner, Pierre Fabre.
• First and only treatment for a rare blood cancer called Epstein‑Barr virus positive post‑transplant lymphoproliferative disease (EBV+ PTLD).
• The FDA granted Priority Review for the Gamida BLA and has set a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2023 as an allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers

2 – Approvals Second Line Large B Cell Lymphoma

• Historic after going head-to- head against decade long standard of care, hematopoietic stem cell transplant, and beating it!
• Gilead/Kite Yescarta was the first CAR-T available in the second-line lymphoma setting followed by Breyanzi
• Patients able to start on Yescarta after failing first-line chemo or relapsing within 12 months of chemotherapy
• CAR-T’s described as curative for first time

1 – Limited Patient Access Post Approval

The EU Market is Experiencing Challenges

• 7 of 24 approved products have been withdrawn from the European Market
• Reimbursement, or inadequate value assignment, has caused companies such as bluebird bio to exit the market

US and EU

• Regulatory structure built on maintenance drug model
• Modernization is crucial to patient access

Flexibility

• Regulators – continue to modernize legislation and market uptake will decide
• Manufacturers – scale to meet demand and payment on success
• Payors – modernize using mechanisms such as pre-approval and value-based contracting