In this video you'll hear about the key differences to think about when you're interacting with Cell and Gene companies compared to small molecule and recombinant protein drug developers.
Nick Stephens, President of The RSA Group, shares his observations on the patient-centric mission that Cell and Gene companies tend to have.
Janel Firestein from Clarkston Consulting shares her experiences around the higher data and digital needs that Cell Therapy companies tend to have, because of their need for transparency in the supply chain.
Sergio Armani, VP Business Development at Advarra, shares some of the challenges he sees from his vantage point related to the clinical complexity of running a gene therapy study. Sergio also shares guidance on IBC Reviews.
2.1. Yes. They are working on cancer. What type of cells are they administering in their oncology therapy?
2.1.1.. Dendritic cells. Are the dendritic cells the patient receives derived from her/his own cells?
18.104.22.168. No. They are donor-derived cells (allogeneic). An example here of allogeneic dendritic cells is Lineage Cell Therapeutics' VAC2 Product.
22.214.171.124. Yes. The cells are from the patient (autologous). An example here of a company working on autologous dendritic cells is APAC Biotech.
2.1.2. T-Cells. Are the T-cells being genetically modified prior to the patient receiving them?
126.96.36.199 No. Sometimes this is referred to as 'optimized' or 'non-engineered.' Are the T-cells being used to target solid tumors or blood cancers?
188.8.131.52.1 Solid Tumors. Examples here include InstilBio's ITIL-168 and Iovance's LN-144.
184.108.40.206.2 Blood cancers. An example here is NexImmune's NEXI-002, which the company is using to target Multiple Myeloma.
220.127.116.11. Yes, the cells are being genetically modified. This is sometimes referred to as "engineered.' What type of genetic modification is made to the T-cells?
18.104.22.168.1 Other genetic modifications. Immatics/ TCR bispecifics. KSQ / KSQ-001
22.214.171.124.2 Chimeric Antigen Receptor (CAR) gene(s) added: CAR-T. Are the T-cells the patient receives from her/his own cells?
126.96.36.199.1.1 No. From Donors Allogeneic CAR-T (newer fields). Precision Biosciences / PBCARD191 (targets CD19)
188.8.131.52.1.2 Yes. Autologous CAR-T “Classic CAR”. Are they targeting a Hematological condition? (blood cancer)
184.108.40.206.1.2.1 Yes. Blood cancer. (aka liquid tumors). What is the (antigen) target of the chimeric antigen receptor (CAR)?
220.127.116.11.18.104.22.168 CAR-T Examples Targeting BCMA.
22.214.171.124.126.96.36.199.1 Legend Biotec / Cartitude-1 Program.
188.8.131.52.184.108.40.206.2 Arcellx / CART-ddBCMA
220.127.116.11.18.104.22.168 CAR-T Example Targeting CD20
22.214.171.124.126.96.36.199.1 MustangBio / MB-106
188.8.131.52.184.108.40.206 CAR-T Examples Targeting CD38 molecule on cancer cells
220.127.116.11.18.104.22.168.1 Celgene Bristol Myers Squibb Company. Abecma (idecabtogene vicleucel). FDA Approved.
22.214.171.124.126.96.36.199 CAR-T Examples Targeting CD19 molecule on cancer cells
188.8.131.52.184.108.40.206.1 Kite a Gilead Company. Yescarta. FDA Approved.
220.127.116.11.18.104.22.168.2 Kite a Gilead Company. Tecartus. FDA Approved.
22.214.171.124.126.96.36.199.3 Novartis. Kymriah. FDA Approved.
188.8.131.52.1.2.2 No. Solid tumors. MustangBio / MB-103 (targets HER2)
2.1.3. NK Cells (Natural Killer Cells). Are the NK cells being genetically modified prior to the patient receiving them?
184.108.40.206 No. Celularity / CYNK-001. Artiva / AB-101.
220.127.116.11 Yes. Some Genetic Change. Are the NK cells being programmed to express a Chimeric Antigen Receptor?
18.104.22.168.1 Yes. “CAR NK”. Artiva / AB-201 [HER2]. Nkarta Therapeutics / NKX019. Cytovia Therapeutics / CYT-503. ONK Therapeutics / ONKT101.
22.214.171.124.2 No. Other genetic manipulations. Shoreline / preclinical programs. Coeptis Pharmaceuticals / CD38-GEAR-NK (autologous).
2.1.4 Other cell types
126.96.36.199 Immunovative Therapies Ltd. / AlloStim
188.8.131.52 Acepodia / “ACE1831” (y/8 T-cells)
184.108.40.206 Geneta Science / Temeferon (HP stem cells)
2.2. No. Are the cells used for some sort of regeneration treatment?
2.2.1 Yes. Targeting regeneration and repair. Where are the cells from?
220.127.116.11 Other cell types
18.104.22.168 iPSCs. What disease/tissues is the company targeting?
22.214.171.124.1 Liver disease. GC Liver Therapeutics / Hepatocyte product
126.96.36.199.2 Muscular dystrophies. Vita Therapeutics / VTA – 110
188.8.131.52.3 Cardio. Spark Therapeutics / Preclinical candidates
184.108.40.206 Cardiac fibroblasts
220.127.116.11.1 Cardio > Ischemic Heart Dis. Metcela / MTC001
18.104.22.168 Example: sickle cell disease. Graphite Bio / GPH101 - (HSCs modified with functioning version of beta globulin)
22.214.171.124 Example: infectious diseases.
126.96.36.199.1 Respiratory infections Allo Vir – ALVR106
188.8.131.52.2 Infectious diseases > HIV – Antion Biosciences – anti-HIV CAR-T2. Talks about making genetic changes or uses "gene therapy" terminology. Does the genetic alteration get either incorporated into the cell’s DNA or get replicated to future copies of the cell?
2.1 No. Fake out? Not technically a gene therapy. More accurately a Nucleic-acid based therapy or Therapeutic Nucleic Acid.
2.1.1 e.g. The Pfizer and Moderna COVID mRNA vaccines.
2.1.2 Dyne Therapeutics – siRNA enters the cell nucleus but does not alter DNA.
2.2 Yes. Okay, a legit gene therapy. Do they talk about adding a fully working copy of a faulty gene or instructions for a brand new protein?
2.2.1 No new genes. Just tweaks to existing. Additional genes are NOT added to the genome or passed on during cell division. “GENE EDITING”. Targeted breaks are created. Are instructions to repair the breaks given?
184.108.40.206 No. Instructions to repair the break are not given. GENE INACTIVATION (aka silencing knockout or knockdown). How is the genetic material or therapeutic reaching the cells?
220.127.116.11.1 Adeni-Associated Virus (AAV)
18.104.22.168.1.1 Heart Disease> PCSK9 gene. Precision Biosciences
22.214.171.124.2 Lipid nanoparticle “LNP”
126.96.36.199.2.1 Heart Disease> PCSK9 gene. Verve Therapeutics / VERVE-101
188.8.131.52 Yes. Instructions ARE given to correct the function of the gene. GENE INSERTION – new genetic material added during the edit. Is the therapy applied to cells while the cells are inside the patient’s body?
184.108.40.206.1 No. Outside the body (“ex vivo”) Technically a Cell-based Gene Therapy.
220.127.116.11.1.1 Sickle cell disease. Graphite Bio / GPH101-(HSCs modified with functioning version of beta globulin)
18.104.22.168.2 Yes. “In vivo”. How is the genetic material or therapeutic reaching the cells?
22.214.171.124.2.1 Adeno-Associated Virus (AAV)
126.96.36.199.2.1.1 Metabolic> MMA. LogicBio Therapeutics / LB-001
188.8.131.52.2.2 Lipid nanoparticle “LNP”
184.108.40.206 GENE CORRECTION – no new material added. How is the therapeutic reaching the cells?
220.127.116.11.1 Adeno-Associated Virus (AAV)
18.104.22.168.1.1 Musculoskeletal> DMD. Precision Biosciences
22.214.171.124.2 Lipid Nanoparticle “LNP” (aka non-viral)
126.96.36.199.2.1 Liver > Glycogen storage dis. Beam Therapeutics / Preclinical program
188.8.131.52.3.1 Hemat. > Sickle Cell Disease. Beam Therapeutics / BEAM-101
2.2.2 Yes. “GENE ADDITION”. Is the therapy applied to cells while the cells are inside the patient’s body?
184.108.40.206 Yes. Takes place in Vivo. How is the genetic material or therapeutic reaching the cells?
220.127.116.11.1 Adeno-Associated Virus (AAV)
18.104.22.168.1.1 Musculoskeletal> SM. Novartis. Zolgensma. FDA Approved
22.214.171.124.1.2 Ophthalmology > AMD. Gyroscope Vision for Life / GT-005
126.96.36.199.1.3 Metabolic>Diabetes. Kriya Therapeutics / KT-A112
188.8.131.52.2.1 Oncology. Umoja Biopharma / In Vivo CAR-T (new field)
184.108.40.206.3.1 Generation bio / preclinical programs
220.127.116.11 No. It takes place Ex Vivo. Technically a cell-based gene therapy. Is the gene encoding a chimeric antigen T-cell receptor?
18.104.22.168.1 No. Some other gene is being added. Try starting frsh but heading down the Cell Therapy Path.
22.214.171.124.2 Yes. Go to CAR-T.
126.96.36.199.2.1 Infectious Diseases > HIV. Antion Biosciences / anti-HIV CAR-T.
188.8.131.52.2.2 Chimeric Antigen Receptor (CAR) gene(s) added: CAR-T. Are the T-cells the patient receives from her/his own cells?
184.108.40.206.2.2.1 No. From Donors Allogeneic CAR-T (newer fields). Precision Biosciences / PBCARD191 (targets CD19)
220.127.116.11.2.2.2 Yes. Autologous CAR-T “Classic CAR”. Are they targeting a Hematological condition? (blood cancer)
18.104.22.168.22.214.171.124 Yes. Blood cancer. (aka liquid tumors). What is the (antigen) target of the chimeric antigen receptor (CAR)?
126.96.36.199.188.8.131.52.1 CAR-T Examples Targeting BCMA.
184.108.40.206.220.127.116.11.1.1 Legend Biotec / Cartitude-1 Program.
18.104.22.168.22.214.171.124.1.2 Arcellx / CART-ddBCMA
126.96.36.199.188.8.131.52.2 CAR-T Example Targeting CD20
184.108.40.206.220.127.116.11.2.1 MustangBio / MB-106
18.104.22.168.22.214.171.124.3 CAR-T Examples Targeting CD38 molecule on cancer cells
126.96.36.199.188.8.131.52.3.1 Celgene Bristol Myers Squibb Company. Abecma (idecabtogene vicleucel). FDA Approved.
184.108.40.206.220.127.116.11.4 CAR-T Examples Targeting CD19 molecule on cancer cells
18.104.22.168.22.214.171.124.4.1 Kite a Gilead Company. Yescarta. FDA Approved.
126.96.36.199.188.8.131.52.4.2 Kite a Gilead Company. Tecartus. FDA Approved.
184.108.40.206.220.127.116.11.4.3 Novartis. Kymriah. FDA Approved.
18.104.22.168.22.214.171.124 No. Solid tumors. MustangBio / MB-103 (targets HER2)