CGTLive's 2023 Pillars of Progress: Most-Watched Expert Interviews

For all of 2023, the CGTLive^™ team was following along the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and major medical meetings, the team spent all year bringing the latest information to the website's front page. Although our team covered updates from many major medical society meetings this year, we also reached out to experts outside the context of the conference cycle to seek their insight on recent company announcements, to get their perspective on a disease awareness day, or to simply learn more about a particular gene or cell therapy in the pipeline.

Here, we'll highlight some of the most-watched interviews from CGTLive's Videos page this year that were not directly related to ongoing medical conferences. Click the buttons to watch.

Ben Creelan, MD, on the Potential of Cell Therapy in Non–Small Cell Lung Cancer

• There is a great need for continued development of new treatments for NSCLC.
• Creelan discussed the current state of care in NSCLC and cell therapy’s potential to change this landscape.
• He spoke about 3 different approaches to cell therapy that show promise: tumor infiltrating lymphocyte (TIL) therapies, bispecific T-cell engagers that target tumor-specific antigens, and claudin antigen-directed CAR-T therapies.

The current standard of care for stage 4 non–small cell lung cancer (NSCLC) is a combination treatment consisting of repeated dosing with carboplatin, pemetrexed, and pembrolizumab. Unfortunately, the progression-free survival (PFS) rate at 5 years for patients in this population is only 7%.

"So, if we can get memory T-cells specific against tumor antigens that are able to continually patrol and destroy tumor cells as they arise over the course of decades, we have a better chance of getting a real meaningful regression of cancers.”

— Ben Creelan, MD of Moffitt Cancer Center

Matthew Gornet, MD, on Treating Degenerative Disc Disease With Cell Therapy

• Investigators found that participants with DDD dosed with high-dose (9,000,000 cells/mL; n=20) IDCT had statistically significant improvements in back pain scores by over 30% as measured on a 100mm Visual Analog Scale at 52 weeks (–62.79%, P = .0005).
• CGTLive spoke with investigator Matthew Gornet, MD, spine surgeon at The Orthopedic Center of St. Louis, to learn more about the DGX-A01 study and the recent data presented from it.
• He discussed the treatment landscape of DDD so far and the potential of IDCT and other cell therapies to revolutionize it.

IDCT (rebonuputemcel; DiscGenics) yielded durable improvements in low back pain, function, quality of life, and pain medication usage by 12 weeks in patients with lumbar degenerative disc disease (DDD) in 2-year data from the phase 1/2 DGX-A01 study (NCT03347708).

“I have never seen anything regrow a disk, but I've seen DiscGenics’ cellular therapy do it and we were able to show that in our data also. The high dose group showed dramatic improvement, visibly and from a mathematical computation, showing that disk volume increased. These are signs that we're actually regenerating the spine, which should excite everyone.”
— Matthew Gornet, MD, of The Orthopedic Center of St. Louis

Sukumar Nagendran, MD, on Addressing Unmet Needs in Rett Syndrome With Gene Therapy

• As a monogenic disorder, gene therapy is an area of potential for Rett syndrome, and multiple gene therapies are currently being developed for the disorder.
• One of these is Taysha Gene Therapies’ TSHA-102, an investigational adeno-associated virus vector-based gene therapy currently being evaluated in the phase 1/2 REVEAL clinical trial (NCT05606614).
• Following the announcement of initial results from the dosing of these first 2 participants in REVEAL, CGTLive™ sat down with Sukumar Nagendran, MD, the president and head of research and development at Taysha, to learn more about the therapy and the trial.

Historically, the standard of care for Rett syndrome has largely consisted of physical therapy and speech therapy intended to ameliorate symptoms, as no FDA-approved specifically-targeted drugs existed for the condition. Earlier this year, however, Acadia Pharmaceuticals’ trofinetide (marketed as Daybue) was approved by the FDA for the treatment of Rett syndrome.

“TSHA-102 is a gene therapy given intrathecally into the lumbar area between L4 and L5. It's a simple procedure done by lumbar puncture. That allows it to be done in multiple sites in many parts of the country, even in an outpatient setting, inpatient setting, or in a hospital, etc. Ease of use is paramount here...”

— Sukumar Nagendran, MD, of Taysha Gene Therapies

Michael Kelly, PhD, on Continuing Progress With Gene Therapy in Muscular Dystrophy

• CGTLive spoke with Michael Kelly, PhD, chief scientific officer, CureDuchenne, about the progress to date in the changing treatment landscape of Duchenne muscular dystrophy (DMD) and other dystrophies.
• He discussed the first-of-its-kind FDA approval of Elevidys and other milestones he is looking forward to in the field coming up in the next year.
• These included data readouts from a couple different trials evaluating investigational gene therapies from Pfizer, Solid Biosciences, and other companies.

September is Duchenne Action and Muscular Dystrophy Awareness Month, and CGTLive is speaking with clinicians and advocacy groups in the space to learn more about the progress in the field to date and unmet needs that remain. While 2023 has seen lots of progress in the treatment landscape of the field, including the summer approval of delandistrogene moxeparvovec (marketed as Elevidys by Sarepta), the field’s first gene therapy, more work always remains to be done.

“Some of the concerns that we have today are with these very high dose serious adverse events, that's one of the challenges with Duchenne. When you think that the body is comprised of 40 to 60% muscle – the amount of AAV that we need to put in the body in order to target all the different muscle groups is extremely high."
— Michael Kelly, PhD, of CureDuchenne

Brett Kopelan, MA, on the Future Treatment of Epidermolysis Bullosa With Advanced Therapeutics

• In observance of EB Awareness Week, which is held each year from October 25 to 31, CGTLive™ spoke with Brett Kopelan, MA, the executive director of the Dystrophic Epidermolysis Bullosa Research Association (debra) of America.
• Kopelan spoke about Abeona Therapeutics’ EB-101, an investigational autologous cell therapy intended to treat recessive dystrophic epidermolysis bullosa (RDEB) and Castle Creek Biosciences’ dabocemagene autoficel (FCX-007, D-Fi), an investigational autologous ex vivo fibroblast therapeutic agent delivered by intradermal injections.
• Kopelan also mentioned that debra is working with a company in Germany on a systemic cell therapy approach to treating EB.

Epidermolysis bullosa (EB), a collection of rare genetic connective tissue disorders, remains highly difficult to manage for patients: until very recently, treatment for these disorders was mostly limited to palliative care. Fortunately, this is already changing, with the recent approval of Krystal Biotech’s beremagene geperpavec (B-VEC, marketed as Vyjuvek), a topical and redosable gene therapy for dystrophic epidermolysis bullosa (DEB), in May 2023, and a number of still-investigational advanced therapies on the near-term horizon.

“I think when we are discussing being able to treat this disease effectively, we really need to look at a holistic approach to it... I can see in the near future where a patient is actually using more than one cell and gene therapy.”
— Brett Kopelan, MA, of debra of America