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Technology Name:  Cytomegalovirus Therapeutic Vaccine – Glioblastoma and other cancers 

Company Background

Annias Immunotherapeutics, Inc., is a biopharmaceutical company focused on the development of novel immunotherapeutic approaches to treat cancer.  The company was founded in 2009 by Senior Investigators at the Duke Medical Center and is led by CEO Reiner Laus, MD. It is based on a patented and proprietary immunotherapeutic platform, discovered by John Sampson and Duane Mitchell at Duke University that targets human Cytomegalovirus (CMV). CMV is over-expressed in a variety of human cancers including significant and homogeneous expression in almost all glioblastoma (GBM) but not in normal brain tissue.  Annias Immunotherapeutics is focused on this promising opportunity to utilize CMV proteins as tumor-specific targets.  Additionally, the company has developed superior methods to immunize humans against cancer, and has already tested this approach in human clinical trials. This novel immunotherapeutic platform has shown extraordinary promise in eradicating GBM with virtually no toxicity experienced in the treated patients.

Technology Overview

Annias has exclusive rights to the next generation of proprietary immunotherapeutic platforms for peptide-based and dendritic cell approaches developed at Duke by Senior Investigators in the Preston Robert Tisch Brain Tumor Center who have completed two consecutive clinical trials using CMV pp65 loaded dendritic cells (DCs) in patients with GBM. The first of these trials was randomized and blinded and demonstrated the induction of CMV-specific immunologic responses along with remarkable progression-free (PFS) exceeding 36.6 months vs. 10.8 months for the control group and a median overall survival (OS) exceeding 36.6 months vs. 18.5 months for the control group.  The CMV vaccine is currently being reformulated into a cutting-edge rationally designed multi-epitope peptide conjugate, PEP-CMV. This proprietary technology platform combining chemotherapy and vaccination will be used to clinically evaluate the efficacy and immunologic effects of PEP-CMV vaccines in patients with newly diagnosed GBM. The poor prognosis for patients with GBM will enable Annias to obtain efficacy data from a randomized, controlled trial within two years of trial initiation. Product candidates based on this platform can be rapidly advanced in breast cancer, prostate cancer, and colorectal cancer.

Market Potential

Despite aggressive treatment, GBM remains uniformly lethal with median survival rates for patients with GBM being less than 15 months from the time of diagnosis. Thus, there is a large and urgent need for improved therapies for GBM. World-wide sales of the chemotherapeutic temozolomide (Temodar®) for GBM have reached one billion dollars in spite of its very limited efficacy. The markets for the products in the Annias pipeline for treatment of breast, colorectal, and prostate cancer present multi-billion dollar opportunities.

Competitive Advantage

The recent discovery and confirmation by five independent laboratories, that CMV propagates within a high proportion of GBMs, without infecting surrounding normal brain tissue provides an unparalleled opportunity to utilize the highly immunogenic antigens from CMV as tumor-specific targets. A distinct advantage of immunotherapeutic targeting of viral antigens is that the immune system is better equipped to target viral antigens compared to autoantigens. The frequency of CMV-specific T-cells is several orders of magnitude higher than what can be achieved with approaches targeting autoantigens.

Financial Overview

Annias secured $246,000 in NCI Phase I SBIR funding in 2012 and has recently submitted a Phase II application for $1.9 million. Through the Duke University Medical Center, several million dollars were secured in grant funding for CMV-targeted vaccine research.  The company expects that taking PEP-CMV through a randomized Phase II program, developing its pipeline products, and operating the company over the next four years will require significant incremental investment.

Intellectual Property

The company has exclusive rights to the Duke University portfolio of Immunotherapy patents. This portfolio includes both issued and pending patents, as well as published and as of yet unpublished patent applications. The issued patent includes claims that cover Annias approach both broadly (immunotherapy of cancer by targeting CMV) and narrowly (composition of PEP-CMV therapeutic).

Commercialization Strategy

Annias plans to start the next clinical trial for PEP-CMV this year. The initial capitalization of the company will serve to conduct and collect data from a large-scale, randomized controlled clinical trial for PEP-CMV. This trial will position the company well for product registration, partnering, and further development of its pipeline in additional diseases.

Pipeline Products

The company is developing PEP-CMV with GBM as the lead indication. Follow-on indications that can be targeted with the same product include the four leading cancers: prostate, breast, lung, and colorectal cancer.

Management Team

• CEO and President Reiner Laus, MD. Dr. Laus has worked on developing cancer immunotherapeutics for over 20 years. He was most recently CEO of BN Immunotherapeutics and prior to that he was VP of R&D at Dendreon, where he was a co-inventor of Provenge.
• Chief Scientific Collaborator and Founder, John Sampson, MD, PhD, is leader of the Neuro-Oncology Program at Duke University and head of the Brian Tumor Immunotherapy Program there. He has published extensively on CMV as a tumor-specific antigen and immunotherapy approaches. His laboratory at Duke developed the EGFRvIII-targeted vaccine which is now completing worldwide Phase III trials in patients with GBM.
• Vice president and corporate secretary James Sheldon was founder of Embrex, Inc. (acquired by Pfizer) and EnSys, Inc. (merged into SDOI).

Technology Name: Intraoperative cancer imaging system

Company Background

The Lumicell Imaging System combines a hand-held, single-cell detection imaging device and a cancer-specific molecular imaging agent (LUM015) for real-time identification of residual cancer in the patient’s tumor bed. The system provides surgeons with visual information to perform a thorough removal of residual cancer cells, thus eliminating the need for repeat surgeries due to positive margins or local recurrence.

Technology Overview

The Lumicell Imaging System is a clinical-stage intraoperative technology for detecting and guiding the removal of all residual cancer during the initial surgery. After the initial breast cancer surgery over 35% of patients undergo a second surgery due to residual cancer.  LUM015, which is injected several hours prior to surgery, emits a fluorescence signal having been activated by cancer enzymes in and around the tumor cells. Lumicell’s imaging head is a hand-held device designed for maneuverability in the tumor bed providing seamless operation within the existing surgical workflow. The system uses Lumicell’s proprietary detection algorithm to highlight regions containing residual cancer in a computer display.

Market Potential

Lumicell addresses the unmet need for locating microscopic residual cancer and guiding its removal during the initial surgery. Lumicell is in human clinical trials for breast cancer and sarcoma and have IRB approval to begin trials in esophageal and colon cancers. The U.S. market for Lumicell is a combined $1.43 billion for breast, lung, prostate, colon, esophageal, ovarian, and brain cancers and sarcoma. Most large cancer practices are at risk for the cost of the second surgery and view Lumicell’s product as an immediate financial benefit. The cost savings to the hospitals together with expected additional reimbursement for the guided surgery procedure ensures attractive revenues to Lumicell.

Competitive Advantage

A number of devices attempting to detect cancer without an imaging agent have shown poor sensitivity (below 60%) and specificity (below 40%) and struggled to be adopted. Other competitors are developing comparable technology using an imaging agent and device, but Lumicell is far along in the development process having successfully completed a Phase I clinical trial that demonstrates safety and preliminary efficacy (91% sensitivity and 86% specificity). In contrast with competitors’ imaging agents, LUM015 is also specific to cells at the tumor margin, which reduces the dose requirement and increases the signal to background ratio. Unlike the same-day injection of LUM015, some competitors attempting to use antibody-based agents, which take days for clearance, require an extra visit to the clinic by the patient in advance of the surgery. The handheld device, which is insensitive to surgeon’s and patient’s motion, has unprecedented detection of sub-millimeter residual cancer in a large field of view.

Financial Overview

Lumicell is very capital efficient and has raised $6.7 million in Series A and B venture capital funding. Through NSF and NCI SBIR programs, Lumicell has been awarded $2.4 million. The company has also received a $1 million Massachusetts Life Sciences Accelerator Loan, and our academic and clinical collaborators have received about $1.6 million in funding to support pre-clinical and clinical studies with the Lumicell system.

Intellectual Property

Lumicell has obtained an exclusive license from MIT for the use and commercialization of the imaging device. The company also has an expansive IP portfolio (U.S. and international) including specific architectures of imaging agents, methods for labeling the tumor margin, and a novel laser ablation technology for instantaneous and precise removal of residual cancer.

Commercialization Strategy

Lumicell has secured funds to finance operations through the pivotal trial (2015) and expects to raise $10 million upon FDA product marketing approval (PMA) in late 2015 for product launch.

Regulatory strategy and Pipeline Products

Lumicell’s LUM015, combined with our first device, has completed a Phase 1 safety study at Duke University Medical Center. Lumicell’s combination product has been assigned to the device group (CDRH) of the FDA. Lumicell has completed a pre-IDE meeting with the FDA to discuss upcoming trials in breast cancer.  Lumicell aims for FDA approval under a PMA in breast cancer by late 2015. In parallel, Lumicell has developed a laser ablation module to perform precision surgeries required in brain and ovarian cancers. Lumicell has a pipeline of imaging agents offering further benefits including higher signal-to-background ratios, higher specificity for certain types of cancers and at lower doses.

Management Team

• David Lee, CEO and co-Founder, has 25 years of demonstrated success in product development at Arthur D. Little and has experience running R&D groups and early commercialization of products. He is a co-Founder and the founding CEO of T2 Biosystems, Inc. (NASDAQ:  TTOO) which is about to enter the market.
• Jorge Ferrer, Ph.D., Director of R&D, developed the original imaging system and LUM015. He has 8 years of experience in research, development, and project management.
• David Strasfeld, Ph.D., Senior Scientist, trained in physical chemistry, instrument design, and experimentation, leads the device development efforts.

Company Background

StemMed is a pre-clinical stage drug discovery, development, and testing company that is developing C188-9, a first-in-class, oral inhibitor of signal transducer and activator of transcription (Stat) 3, for treatment of ER-, PR-, HER2- (triple negative) breast cancer (TNBC). StemMed also provides state-of-the-art pre-clinical drug testing services using a panel of 44 breast cancer patient-derived xenograft (PDX) models developed from a diverse patient population, which includes 23 PDX models derived from patients with TNBC; 4 pancreatic cancer PDX models also are available.

Technology Overview 

Stat3 plays a central role in breast cancer stem cell development and has been validated as a drug target in these cells, as well as in the treatment of TNBC, for which no targeted therapy exists. StemMed used computer-based docking to screen 920,000 compounds and identified three small-molecule probes that targeted the phosphotyrosyl peptide-binding pocket within the Src homology 2 domain of Stat3. The most active probe, C188, reduced TNBC PDX tumor volumes and improved tumor-free survival of engrafted mice 4-fold when used in combination with standard chemotherapy. StemMed performed 2-D similarity screening, 3-D pharmacophore analysis, and 3-rounds of structure-activity relationship (SAR)-directed medicinal chemistry to identify C188-9, its lead, first-in-class drug for targeted treatment of TNBC.

Market Potential

The first patients that will be targeted to receive C188-9 will be those patients with locally invasive, metastatic, or treatment-refractory TNBC. An estimated 230,480 new cases of invasive breast cancer were diagnosed in the United States in 2011. Of these, ~40,000 will suffer breast cancer recurrence including 50% of those with TNBC. Unfortunately, standard therapies cannot eradicate the disease and these patients succumb to metastatic disease with a median survival of 2 years. The size of the U.S. market for C188-9 for metastatic/refractory TNBC on a yearly basis is ~20,000 cases for 7 cycles, or a total of 140,000 cycles. C188-9 will be administered orally once daily in the interval between cycles of first-line chemotherapy. Using a conservative figure of $2,000 per cycle, the income generated from 140,000 cycles of C188-9 would be $280 million.

Competitive Advantage

There are two orally bioavailable, small-molecule competitors of C188-9 in development, BP-1-102 and HJC0123. BP-1-102’s modest potency coupled with its low MTD will make it challenging to establish a safe and effective dose of BP-1-102 in humans. HJC0123’s mechanism of action has not been established and the mouse toxicity data presented in the original report was very limited. Other oral agents under development have mechanisms of action that are not understood, substantial toxicity, and did not demonstrate an efficacy signal in Phase I studies.

Financial Overview

StemMed’s drug testing revenue since 2010 totals $913,000. Revenue from STTR grant awards totals $417,000. StemMed also received $100,000 from PDX licensing and $213,000 from partner contributions.

StemMed needs $1 million in external funds for IND-enabling safety and PK studies and for IND filing.

Intellectual Property

StemMed has an exclusive license to ten patents issued to, or filed by, BCM and ownership of composition for C188-9. StemMed also has an exclusive license to use all 48 PDX models for drug testing services, as well as sublicensing to other companies for their in-house use.

Commercialization Strategy

StemMed’s objectives for the next two years are to continue developing its lead product candidate C188-9 by taking it through various studies. StemMed is also in discussions with Atara Biotherapeutics regarding licensing C188-9 for use in cachexia in chronic kidney disease.

Pipeline Products

StemMed has compelling pre-clinical results in cancer cell line xenograft models that also support the use of C188-9 either alone or with radiation therapy in patients with non-small cell lung cancer and head and neck squamous cell cancer. In addition, results from mouse pre-clinical models support its use in patients with cachexia secondary to chronic kidney disease or cancer, and in patients with idiopathic pulmonary fibrosis, scleroderma, inflammatory bowel disease, asthma, and immediate-type hypersensitivity reactions.

Management Team

• President, CEO, and director of drug discovery and development, David Tweardy, MD, discovered key molecular and cellular features of Stat3 during his 28-year research career supported by NIH and other extramural funding totaling over $16 million as PI.
• Vice president and director of drug testing, Michael Lewis, PhD, is an expert in breast cancer biology and developer of 48 breast and pancreatic cancer PDX models whose 15 year research career has been supported by NIH and other extramural funding totaling over $11 million as PI.
• Consultant and vice president of Texas BioAlliance, Jeffrey Larson, PhD, is a drug developer with extensive experience in pharmaceutical, biotechnology, and contract research industries, as well as a record of successful early- and late-stage regulatory meetings with the FDA.
• Consultant and Principal of Soller Regulatory & Research Services, R. William Soller, PhD, has extensive regulatory experience including serving as team leader and lead presenter for over 60 FDA or advisory committee meetings on drug development or postmarketing issues.