Genetically Modified T-cells: Gene Therapy Is Back!
Here are some quick notes and an overview of the companies at Bio:
Immuno-Oncology is one of the hottest new areas of biopharmaceutical development and on October 7 BIO presented a Therapeutic Session on “T-Cell Therapies: Best Bets in Pushing Down the Cost Curve and Prioritizing Cancer Targets”. The panelists included Officers from four emerging companies moderated by Kristen Hege, MD and Assistant Professor from UCSF.
T-cell therapies have been under development for quite some time because of the potential for utilizing the body’s own immune system to create a “living drug” delivering personalized cancer therapy. CAR-T methods as they are known (CAR means chimeric antigen receptors) extract, reengineer and reintroduce a given patients T-cells to provide highly personalized in vivo therapy. Genes that recognize specific cancer cells are reprogammed into the T-cell utilizing a disabled virus. The presumed advantage of engineered T-cells is a living drug is created that does exactly what you want with 90% effectiveness in comparison to drugs targeting proteins and receptors such as PD-1 inhibitors which may be only 50% effective. Moreover because treatment is personalized it would be more cost effective than “pills” if T cell therapy lasts long term with fewer side effects.
Like any new drug technology there will be issues in development and commercialization such as an overactive immune system, cross -reactivity of antigens targeted and cost/scale-up of the autologous cell engineering. And dosing will be critical. Regulatory hurdles should be lessened as the FDA has a lot of experience in this field and has designated CAR a “breakthrough” designation.
We are now closer to the potential of therapeutic breakthroughs as exemplified by these clinical stage companies in the session:
bluebird bio, Inc. (BLUE) : Price: $37.23 Market Cap $1.06B
Focuses on gene therapy for severe genetic and orphan diseases. Most advanced candidate is Lenti-D which is in Phase II/III studies for treatment of childhood cerebral adrenoleukodystrophy. Two other Phase I/II products are in the hematologic disease pipeline as well as a CAR-T oncology pre-clinical program with Celgene (CELG).
GlobeImmune Inc. (GBIM) : Price :$4.67 $26.55M
Has a targeted molecular immunotherapy platform called Tarmogen which stimulates T-cells that destroy infected or malignant cells.The pipeline has four clinical stage products in oncology including a partnerships with Celgene (CELG) and two clinical stage products in HBV partnered with Gilead (GILD).
Kite Pharma, Inc. (KITE) : Price $33.69 Market Cap $1.35B
Focuses on the development and commercialization of novel cancer immunotherapy products.Its lead product includes KTE-C19, a chimeric antigen receptors-based engineered autologous cell therapy (eACT) for treatment of B cell lymphoma. There are also three clinical stage programs and other pre-clinical products underway for tumors.
ZIOPHARM Oncology Inc. (ZIOP): Price $2.58 Market Cap $253M
Focuses on discovery and development of cancer therapies that address unmet medical needs utilizing synthetic biology to deliver DNA though a novel gene expression system. Two Phase II programs are underway for breast cancer and melanoma utilizing DNA therapeutics in partnership with Intrexon Corporation.
Another private Company based in the U.K.- AdaptImmune– presented in a separate session. The Company is in a partnership (June 2014) with GlaxoSmithKline plc (GSK) for devloping cell-based therapies and recently announced a $104M Series A Financing led by New Enterprise Associates (NEA). Using its unique T-cell receptor (TCR) engineering technology to target and destroy cancer or infected cells utilizing the bodies own machinery. TCR will target the cancer testis antigen,NY-ESO-1 as well as at least 28 other targets. The Company holds extensive IP for gene therapy utilizing lentivirus vectors as well as a Dynabead license from ThermoFisher (TMO). Cancer trials in the U.S. have begun and will include myeloma,melanoma,sarcoma and ovarian cancer with at least 5 centers expected by 2015. The TCR approach differs from CARs in that antibody targets are not being used, but use internally processed cancer targets.
Immunotherapy will be an exciting field to follow over the long term with breakthrough therapies for treatment of cancer and infectious disease. Although four of these companies are public we need to look for clinical milestones and deals that offer an entry point for investment. BLUE and KITE have already made big moves and have market caps above $1B. Stay tuned.