Welcome to your Update from the Clinic for the month of September. There’s a mixture of news from the cancer stem cell companies and immunotherapy companies this past month. Amongst other things, the FDA removed the previously imposed partial hold on one of OncoMed’s therapeutics; Opexa Therapeutics announced its next therapeutic program; and, Harvard Apparatus Regenerative Technology, a niche company delivering regenerated organs to patients, obtained an orphan drug designation. Read on to find out more.
OncoMed (OMED), a company developing a plethora of different small molecules and biologics targeting cancer stem cells, announced early in September that the FDA has removed the partial hold placed on clinical studies investigating Ipafricept for a number of cancers, including pancreatic and ovarian. In June of this year, OncoMed voluntarily halted development of the candidate after it was informed by clinical sites that some patients were experiencing mild-to-moderate bone-related adverse events. Enrolment of patients and dosing will recommence over the next few weeks. A set of new study parameters will be used to continue investigating Ipafricept in combination with standard of care.
The Wnt and Notch pathways have been central to OncoMed’s campaign against cancer stem cells. Both Ipafricept and a second product, Vantictumab, – also halted voluntarily – target and inhibit the Wnt pathway. After bringing several biologic candidates into clinical studies, OncoMed is now assembling a number of small molecule candidates at the preclinical stage to mirror its clinical development program. To this end, it announced the selection of its first small molecule candidate to target the Wnt pathway, which will be co-developed with Bayer Pharma AG. OncoMed’s Notch-targeting candidates are being co-developed with GSK and Celgene.
Texas-based Opexa Therapeutics (OPXA) announced its next clinical program, which will target an orphan disease known as Neuromyelitis optica (NMO), which is characterized by demyelination (when the myelin sheath around nerves is damaged) of the optic nerve and spinal cord. Humans with NMO experience swelling, pain, and loss of vision in the eyes, and weakness, paralysis, and loss of sensation in the limbs. The company began preclinical development of OPX-212 earlier this year and hopes to file an investigational new drug (IND) application by mid-2015. It will go after an orphan and fast track designation for the therapy.
Opexa is unique among the cell-based immunotherapy companies. Rather than pursuing cancer, the company has differentiated itself by focusing its clinical development efforts on autoimmune disorders, specifically those that cause demyelination. The company’s ImmPath™ T cell platform allows for the isolation and expansion of myelin-reactive T cells from a patient’s peripheral blood. These cells are then irradiated and injected subcutaneously as a vaccine, eliciting an immune response against the T cell population that causes destruction of myelin. Opexa’s lead therapeutic candidate, Tcelna® (imilecleucil-T), is being investigated for the treatment of Secondary Progressive Multiple Sclerosis in a Phase IIb study, an indication that has one approved therapy (but one that comes with a black box warning for severe cardiotoxicity).
Interestingly, unlike most immunotherapies, administration of Tcelna® is not one-off. Instead, it is envisaged that patients will use Tcelna® annually, such that they maintain an immune response against an evolving dominant myelin-reactive T cell population even if there is an epitope shift to myelin antigens (the T cells begin to recognize different proteins associated with myelin) or the patient’s disease profile changes. The therapy consists of five subcutaneous injections over the course of six months.
Maryland-based Northwest Biotherapeutics (NWBT) has become the first company to receive a “Promising Innovative Medicine” (PIM) designation by the UK authorities. The company has been working feverishly on developing its DCVax-L immunotherapy, which is a dendritic cell-based immunotherapy that will be investigated in a Phase 3 study for glioblastoma multiforme (GBM). The designation is the first part of the UK’s Early Access to Medicine Scheme (EAMS), which was put in place in April 2014, to fast track high impact therapies to severely ill patients. ImmunoCellular Therapeutics (IMUC), which is also developing a cell-based immunotherapy for GBM, ICT-107, received positive news from the FDA that will support the candidate’s advancement into a Phase 3 study. Based on the feedback, IMUC will launch a Phase 3 study in early 2015.
Harvard Apparatus Regenerative Technology (HART) obtained an orphan drug designation from the FDA for its HART-Trachea product, which is being developed to replace or repair a trachea that has been damaged either by way of cancer or severe trauma. The company’s strategy is to target life-threatening conditions that have poor or no available alternative treatment options, thereby making it easier to acquire patient informed consent for treatment and hospital ethics committee or Institutional Review Board approval. Their product, the InBreath™ Airway Transplant System, is composed of a synthetic trachea made from a porous plastic scaffold and a rotating organ bioreactor that is used to seed a patient’s own bone marrow cells onto the matrix prior to transplant. HART plans to combine existing clinical study data from the EU and Russia, with data it will collect in the U.S., to seek regulatory approval of the product.
The UK Promising Innovative Technology designation for Northwest Biotherapeutics is an achievement for the company, and a milestone for cell-based immunotherapy companies. Which countries will be the most supportive of these novel and highly innovative technologies? The UK is clearly working hard to stay at the forefront of life sciences innovation adoption. While fast tracking these therapies through the clinic increases uncertainty around reimbursement decisions, there is a compelling business case to be made in being the first country to adopt innovative life sciences technologies. This is especially so at a time when austerity is affecting health-care systems globally and governments are risk-averse, focusing primarily on cost-containment.
Disclaimer: “Update from the Clinic” is a blog post generated by news flow from public regenerative medicine (RM) companies around the globe. As CCRM has public RM companies in its industry consortium, and the number of such companies is relatively limited on a global scale, Mark Curtis will sometimes include CCRM consortium members in his review. This blog post is provided for general information only and nothing contained in the material constitutes a recommendation for the purchase or sale of any security. The author is not a shareholder of any public RM company. To see a list of CCRM’s industry consortium members, please visit http://ccrm.ca/industry-consortium