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CritiTech PES partner NanOlogy Presents Updated Clinical Data on Targeted Injections of NanoPac® for Pancreatic Cancer and Mucinous Cystic Neoplasms on DDW2020 Site

Updated clinical data from both trials available through Digestive Disease Week® (DDW) Online Education Site

FT. WORTH, (May 14, 2020) — NanOlogy, LLC, a clinical-stage oncology company, announced today that updated data from two of its ongoing clinical trials were presented as abstracts last week through the DDW ePosters and ePresentations site . The clinical trials are evaluating endoscopic ultrasound guided fine needle injection (EUS-FNI) of NanoPac® (submicron particle paclitaxel) suspension for treatment of locally advanced pancreatic cancer (LAPC) and mucinous cystic neoplasms (MCNs/IPMNs) of the pancreas.

The lead author of the abstract on intratumoral NanoPac for LAPC is Neil Sharma, MD (Parkview Cancer Institute – Fort Wayne, IN). The lead author of the abstract on intracystic NanoPac for MCNs/IPMNs is Mohamed O. Othman, MD (Baylor College of Medicine – Houston, TX).

Pancreatic Cancer

The Phase 2a dose-rising and expansion trial is evaluating over 6 months the safety and preliminary efficacy of NanoPac delivered intratumorally by EUS-FNI in patients with LAPC, concurrent with or following SOC therapy for the disease. After completing the dose-rising cohort (n=11), a dose expansion cohort has now fully enrolled (n=22) in which patients receive 2 monthly intratumoral (IT) injections of NanoPac. FDA has also recently allowed expansion of up to 30 additional patients who will receive up to 4 monthly IT injections.

Dr. Sharma’s abstract submitted to DDW in December 2019 reports data from the first 7 evaluable subjects from the dose expansion cohort. No drug-related local or systemic SAEs were reported including no reports of acute pancreatitis in any subject, 4 subjects had a partial response, 2 had stable disease, and 1 had progressive disease. Encouraging data has continued to accrue from the fully enrolled dose expansion (2- injection) cohort, which are expected to be presented later in 2020

Pancreatic Cyst

The Phase 2a dose rising and expansion trial is evaluating over 6 months the safety and preliminary efficacy of NanoPac delivered intracystically by EUS-FNI following aspiration in patients with MCNs/IPMNs. The study has now completed enrollment (n=19) with patients in the dose expansion phase (n=8) receiving two intracystic injections of NanoPac 12 weeks apart.

Dr. Othman’s abstract also submitted in December reports data from the first 9 subjects who had completed the trial. No confirmed drug-related local or systemic SAEs were reported including no reports of acute pancreatitis. Plasma paclitaxel levels have not exceeded 1 ng/mL indicating that NanoPac particles are retained in the cyst over time. Evaluation of cyst volume showed decreases ranging from 8% to 89% in 8 subjects, 6 of whom showed a volume decrease > 50%. Cyst volume increased in 1 subject.

Based on encouraging results from both trials, NanOlogy is designing follow-on clinical protocols for evaluation by FDA.

In 2020, about 57,600 new cases of pancreatic cancer will be diagnosed in the U.S. and 47,050 people will die from the disease. Pancreatic cancer is currently the third most frequent cause of cancer related death in western countries and is predicted to become the second leading cause of death from cancer within the next 10 years. It is one of the few cancers for which no meaningful improvement in survival has been achieved over recent time with only an 8% survival rate at 5 years.

MCNs/IPMNs are a subset of pancreatic cysts that risk progression to pancreatic cancer. While estimates vary widely, as many as 30,000 new cases of high risk MCNs/IMPNs are diagnosed annually in the U.S. These patients may ultimately be required to undergo surgical resection of the pancreas to remove the lesion, a complicated procedure associated with high morbidity. No approved drug therapy exists in the U.S to treat the condition.

In addition to pancreatic neoplasms, NanOlogy clinical programs are advancing in genitourinary, peritoneal, lung, and dermal cancers.

The NanOlogy submicron particle therapeutic platform is based on a proprietary production technology that converts taxane API crystals into stable submicron particles of pure drug with disproportionate size to surface area ratio. The particles are covered by two composition of matter patents (US 9,814,685) and (10,507,195) both valid until 2036 in the US and pending globally.

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About NanOlogy

NanOlogy, LLC (www.nanology.us) is a private clinical stage oncology company formed in 2015 to finance and clinically develop a patented submicron particle technology platform for targeted, sustained delivery of proven drugs aimed at increasing their value in the treatment of cancer and other serious diseases.

Disclaimers

This announcement contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including statements about our product development, business, and other activities. Such statements are subject to the risks and uncertainties inherent in any pharmaceutical development program which may cause actual results to differ materially due to developmental, clinical trial, regulatory, market, competitive, technological, or other factors. All forward-looking statements are made as of the date of this announcement and the company disclaims any intent or obligation to update these statements. NanOlogy investigational drugs have not been proven to be safe and effective as required by U.S. FDA and have not been approved for commercial distribution. NanOlogy and NanoPac are trademarks of NanOlogy LLC.

Media Contact

Dan Eramian
Opus Biotech Communications
danieleramian@comcast.net
425-306-8716

Charles Craig
Opus Biotech Communications
charles.s.craig@gmail.com
404-245-0591

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Video

Video Highlights of NanoPac® Injection for Pancreatic Cancer

Highlights of the presentation by Dr. Neil Sharma, President, Parkview Cancer Institute; Director of Advanced Interventional Endoscopy and Endoscopic Oncology Programs, Medical Director GI Oncology.  View the full 7-minute video here.

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Presentation

ACG 2019 Plenary Presentation: A Novel EUS-guided Intratumoral Delivery of Submicron Particle Paclitaxel for the Treatment of Locally Advanced Pancreatic Cancer

A novel EUS-guided Intratumoral Delivery of Submicron Particle Paclitaxel for the Treatment of Locally Advanced Pancreatic Cancer. A Prospective Safety, Tolerability and Preliminary Efficacy Study.

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CritiTech PES partner NanOlogy’s Clinical Updates on Local Injection of NanoPac® for Pancreatic Cancer and Mucinous Cystic Neoplasms of the Pancreas

Interim data from both clinical trials presented at the 2019 American College of Gastroenterology (ACG) Conference in San Antonio

November 07, 2019 05:30 AM Eastern Standard Time

FORT WORTH, Texas–(BUSINESS WIRE)–NanOlogy LLC, a clinical-stage oncology company, announced today that interim data were presented last week at the 2019 ACG annual meeting from two of its clinical trials each evaluating endoscopic ultrasound guided fine needle injection (EUS-FNI) of NanoPac (submicron particle paclitaxel): one for treatment of locally advanced pancreatic cancer (LAPC) and the other for treatment of mucinous cystic neoplasms of the pancreas (MCNs).

The pancreatic cancer clinical update of intratumoral NanoPac for treatment of LAPC was presented by Simon K. Lo, MD(Cedars-Sinai) as part of the Pancreatic Cancer/Esophagus plenary session.

The Phase 2a dose-rising and expansion pancreatic cancer trial is evaluating the safety and preliminary efficacy of NanoPac delivered intratumorally by EUS-FNI over 6 months in patients with nonresectable LAPC. After completion of the dose-rising phase, the trial has now enrolled 16 of 22 subjects into the dose expansion phase of the trial in which patients are receiving two intratumoral injections of NanoPac 4 weeks apart.

Highlights from Dr. Lo’s presentation on the dose expansion phase of the trial:

  • No drug-related local or systemic serious adverse events have been reported to date (n=25) including no reports of acute pancreatitis.
  • Of 7 subjects who have completed the 6-month study to date, one subject had a partial response with restaging from nonresectable to resectable (see video), 3 had stable disease, 1 had progressive disease, and 2 were withdrawn from the study.
  • Tumor volume decreases ranging from 7% to 76% have been seen in 7 of 11 subjects upon latest mpMRI to date at either the 3- or 6-month time point.
  • CA19-9 reductions of greater than 20% have been seen in 5 of 11 subjects upon latest measure to date at either the 3- or 6-month time point.

The pancreatic cyst clinical update on intracystic NanoPac for treatment of MCNs of the pancreas was presented during the poster sessions by Mohamed O. Othman, MD (Baylor College of Medicine). Dr Othman’s poster was recognized as a Presidential Poster, a distinction given to fewer than 5% of accepted abstracts each year, and was ultimately named co-winner for high quality, novel, unique and interesting research.

The Phase 2a dose rising and expansion pancreatic cyst trial is evaluating the safety and preliminary efficacy of NanoPac delivered intracystically by EUS-FNI following aspiration in patients with MCNs. The study is also enrolling in the dose expansion phase of the study and patients are receiving two intracystic injections of NanoPac 12 weeks apart.

Highlights from Dr. Othman’s poster presentation on the trial:

  • No drug-related local or systemic serious adverse events (SAE) have been reported to date (n=15) including no reports of acute pancreatitis. One case of gastric outlet obstruction that was possibly drug-related occurred in a subject who had a recent unrelated endoscopic procedure for hepatobiliary dysfunction. This condition was subsequently added as an exclusion criterion for the trial.
  • Plasma paclitaxel levels for all subjects analyzed have not exceed 1ng/mL suggesting that NanoPac particles are retained in the cyst over time.
  • Cyst volume decreases ranging from 8% to 89% have been seen in 9 of 11 subjects at last available imaging at either the 3- or 6-month time point.

NanOlogy plans to design follow-on clinical trials for both pancreatic cancer and pancreatic cysts in 2020 to further advance the programs toward regulatory submission.

In 2019, an estimated 57,000 new cases of pancreatic cancer will be diagnosed in the U.S. and 46,000 people will die from the disease. Pancreatic cancer is among the deadliest cancers with 9% survival rate at 5 years. It is also one of the few cancers for which no meaningful improvement in survival has been achieved in the last two decades. MCNs are a subset of pancreatic cysts that risk progression to pancreatic cancer. Patients with high risk MCNs may undergo surgical resection of the pancreas to remove the lesion, a complicated procedure associated with mortality and morbidity rates of 2% and 30% respectively. For both the disease itself and one of its common precursors, NanOlogy investigational drugs may offer a new way to help prevent or treat pancreatic cancer.

In addition to these trials, NanOlogy is advancing its therapeutic platform in preclinical and clinical programs across genitourinary, peritoneal, lung, and dermal cancers. The NanOlogy therapeutic platform is based on a proprietary submicron particle production technology that reduces the size of taxane API crystals by up to 400 times into stable submicron particles of pure drug with exponentially increased surface area and unique geometry. The characteristics of the particles have recently been granted a composition of matter patent valid in the US (9,814,685) and Australia until 2036, and pending globally.

About NanOlogy

NanOlogy, LLC (www.nanology.us) is a private clinical-stage oncology company developing a submicron particle therapeutic platform designed for local delivery to increase the effectiveness of cancer treatment while reducing the serious adverse effects normally associated with systemic chemotherapy.

Disclaimers

This announcement contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including statements about our product development, business, and other activities. Such statements are subject to the risks and uncertainties inherent in any pharmaceutical development program which may cause actual results to differ materially due to developmental, clinical trial, regulatory, market, competitive, technological, or other factors. All forward-looking statements are made as of the date of this announcement and the company disclaims any intent or obligation to update these statements. NanOlogy investigational drugs have not been proven safe and effective as required by U.S. FDA and have not been approved for commercial distribution.

Contacts

Dan Eramian 
Opus Biotech Communications 
danieleramian@comcast.net 
425-306-8716 

Charles Craig 
Opus Biotech Communications 
charles.s.craig@gmail.com 
404-245-0591

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News

CritiTech PES partner NanOlogy™ Completes Dose Escalation Portion of Phase 2 Clinical Trial of NanoPac® for Treatment of Prostate Cancer

  • Intratumoral injection of three concentrations of NanoPac successfully completed across a total of 9 patients
  • Highest concentration of NanoPac continues into dose confirmation phase of trial as no drug-related local or systemic side effects observed
  • Histologic examination of prostate tissue shows tumor regression

FT.WORTH/DALLAS, (April 30, 2018) — NanOlogy LLC, a clinical-stage pharmaceutical development company, has completed the dose escalation phase of an open-label clinical trial of NanoPac (submicron particle paclitaxel sterile suspension) injected directly into the tumor area for treatment of prostate cancer. Successful completion of the dose escalation phase has allowed the highest concentration of NanoPac to begin the dose confirmation phase of the trial, which will continue to generate data on safety and tumor response.

The Phase 2a trial is enrolling patients with local prostate cancer scheduled for prostatectomy. In the trial, patients receive intratumoral injection of NanoPac 28 days before surgery. Tumor volume and prostate tissue biopsy taken prior to NanoPac administration is compared to tumor volume and tissue after surgery.

In the dose escalation phase to determine highest concentration of drug which can be safely administered, 6 mg/mL, 10 mg/mL, 15 mg/mL concentrations of NanoPac were each injected into three patient cohorts followed by safety review for each cohort. No drug related serious adverse events were reported in any of the cohorts and preliminary data show evidence of tumor reduction and tumor cell death.

“NanoPac is injected directly into the cancerous lobe of the prostate under MRI/TRUS fusion guidance”, said Andre Abreu, MD, Assistant Professor of Clinical Urology, Co-director of Image-Guided Surgery & Focal Therapy of Prostate and Kidney Cancer at the University of Southern California’s Institute of Urology. “The drug injected locally has been well tolerated to date and we have progressed into the dose confirmation phase of the trial to further assess safety and tumor response.”

“NanoPac is injected directly into the cancerous lobe of the prostate under MRI/TRUS fusion guidance”, said Andre Abreu, MD, Assistant Professor of Clinical Urology, Co-director of Image-Guided Surgery & Focal Therapy of Prostate and Kidney Cancer at the University of Southern California’s Institute of Urology. “The drug injected locally has been well tolerated to date and we have progressed into the dose confirmation phase of the trial to further assess safety and tumor response.”

The dose confirmation phase has begun and will enroll 9 additional patients for a total of 18 patients who received direct injection of NanoPac 28 days prior to their scheduled prostatectomy. In addition to assessing safety and tolerability, tumor size and histologic evidence of tumor response will be evaluated, and local lymph nodes will be analyzed to investigate potential lymphatic transport of NanoPac. Completion of the clinical trial and final report are expected in the third quarter of 2018.

Prostate cancer affects an estimated 3 million men in the US with about 160,000 new cases and 27,000 deaths annually. Patients at higher risk for disease progression or those in whom the cancer has spread may face surgical removal of the prostate or radiation therapy. Unfortunately, these patients often suffer incontinence or impotence, which significantly decrease quality of life.

Dr. Abreu added, “If we are successful, we may offer a treatment option for moderate or high-risk patients with localized or non-metastatic disease potentially providing better oncologic outcomes while minimizing side-effects of chemotherapy, and therefore maintaining quality of life.”

The prostate cancer study is part of an extensive clinical development program underway by NanOlogy. Local administration of NanoPac is also being evaluated in Phase 2 clinical trials for ovarian cancer (with orphan drug designation), pancreatic cancer, and pancreatic mucinous cysts.

An inhaled version of NanoPac for lung cancer has demonstrated prolonged lung tissue residence time and tumor regression in preclinical studies and a clinical trial of NanoDoce® (submicron particle docetaxel sterile suspension) is planned to begin in September for bladder cancer.

In addition, NanOlogy is progressing a clinical trial of a submicron particle paclitaxel topical anhydrous ointment for cutaneous metastases. The topical product was developed by NanOlogy affiliate DFB Soria, who has also recently completed a Phase 2 clinical trial of the product in actinic keratosis, which showed lesion reduction and no drug-related local or systemic adverse events.

All the NanOlogy and Soria products are progressing under FDA’s streamlined 505(b)(2) regulatory pathway. The NanOlogy submicron particle technology platform is based on a patented production process that reduces the size of paclitaxel and docetaxel API crystals by up to 400 times into stable, naked submicron particles of pure drug with exponentially increased surface area and unique geometry. The particles are so unique they have recently been granted a composition of matter patent (US 9,814,685) which provides NME-like advantages without the risk and timeline associated with new molecular entity drug development.

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About NanOlogy

NanOlogy, LLC (www.nanology.us) is a clinical stage pharmaceutical company formed by DFB Pharmaceuticals, LLC of Fort Worth, TX, CritiTech, Inc. of Lawrence, KS, and US Biotest, Inc. of San Luis Obispo, CA, to finance and clinically develop a patented submicron particle technology platform for local, sustained delivery of proven drugs aimed at increasing their safety and efficacy in the treatment of cancer and related conditions.

Disclaimer

This announcement contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including statements about our product development, business, and other activities. Such statements are subject to the risks and uncertainties inherent in any pharmaceutical development program which may cause actual results to differ materially due to developmental, clinical trial, regulatory, market, competitive, technological, or other factors. All forward-looking statements are made as of the date of this announcement. DFB disclaims any intent or obligation to update these statements. NanOlogy and Soria investigational drugs have not been proven to be safe and effective in accordance with the requirements of the U.S. FDCA and have not been approved by FDA for commercial distribution.

Media Contacts

Dan Eramian
Opus Biotech Communications
danieleramian@comcast.net
425-306-8716

Charles Craig
Opus Biotech Communications
charles.s.craig@gmail.com 
404-245-0591

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Presentation

NanoPac® Inhalation Treatment of NSCLC in a Nude Rat Orthotopic Lung Cancer Model

Background: NanoPac® is patented submicron particle paclitaxel in stable powder form without coating or carrier agents. In a previous PK study, healthy male rats inhaled a single exposure of nebulized NanoPac® (0.37 mg/kg or 1.0 mg/kg) or IV Abraxane® (5.0 mg/kg) with a final necropsy time-point at 14 days. T1/2 of NanoPac® and Abraxane were 56hrs and 20hrs with drug present at 14 days and not after 3 days, respectively. Tissue examined from the last time point were microscopically indistinguishable from non-treated controls.

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Presentation

Targeted Delivery of Submicron Particle Cancer Chemotherapy: Helping Shift the Immunotherapy Paradigm

NanOlogy™, a clinical-stage pharmaceutical development company, was formed in 2015 to increase the effectiveness and safety of CT through targeted delivery. Based on a proprietary submicron particle production technology, the company has developed stable, uncoated submicron particles of the taxanes, paclitaxel and docetaxel, as investigational drugs, which can be administered directly to the site of disease via injection, instillation, or inhalation.

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Presentation

Evaluation of Submicron Particle Docetaxel Directly Injected into Uro-Oncologic Xenografts

Suspensions of submicron particle taxanes (Figure 1) allow for direct administration of high, sustained levels of chemotherapeutics at the site of disease. Intratumoral (IT) injections of submicron particles of pure docetaxel (NanoDoce) into clear cell renal carcinoma (786-O), transitional cell bladder carcinoma (UM-UC-3) and prostate carcinoma (PC-3) xenografts were evaluated.

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News

CritiTech PES partner NanOlogy announces First Patient Enrolled in a Phase 1/2 Clinical Trial of NanoDoce® for Treatment of Bladder Cancer

  • NanOlogy may offer an alternative treatment option for patients with bladder cancer
  • Investigational drug, NanoDoce, is injected locally into tumor resection bed via cystoscope guidance followed by intravesical instillation

April 09, 2019 05:30 AM Eastern Daylight Time

FT. WORTH, Texas–(BUSINESS WIRE)–NanOlogy, a clinical-stage oncology company, today announced the first patient has been enrolled in a clinical trial of NanoDoce (sterile submicron particle docetaxel suspension) for treatment of bladder cancer. The Phase 1/2 dose-rising trial will evaluate the safety and preliminary efficacy of NanoDoce for patients with high-risk non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).

In 2019, an estimated 80,000 new cases of bladder cancer will be diagnosed in the United States and an estimated 18,000 will die from the disease. Despite being one of the top five cancer diagnoses in the U.S., the last drug FDA approved for NMIBC was more than a decade ago. Of all cancers, bladder cancer tends to have the highest lifetime treatment costs due to the frequency of recurrence, progression to MIBC often requiring removal of the bladder (cystectomy), and lifetime cost of care thereafter.

In the NanOlogy clinical trial, following transurethral resection of the bladder tumor, subjects will receive direct injections of NanoDoce into the base of the index tumor resection site in combination with an intravesical instillation of NanoDoce. Additional intravesical instillations of NanoDoce will be administered to NMIBC subjects while MIBC subjects will follow institutional standard of care.

The local delivery of submicron particle docetaxel suspension [NanoDoce] represents an important step in evaluating new therapies for the treatment bladder cancer”, said Dr. Donald Lamm, MD, President of BCG Oncology and principal investigator on the trial. “Preclinical studies suggest the submicron particle technology improves both the penetration of drug into the bladder wall and its duration of activity. If this investigational drug can be proven to delay or prevent disease progression and need for cystectomy, it would contribute significantly to the quality of life of patients with this disease.”

An abstract from preclinical studies of NanoDoce was presented in February at the 2019 Genitourinary Cancer Symposium. In one of the studies, NanoDoce administered via intratumoral injection resulted in prolonged, high concentration of drug in tumor tissue, significant tumor regression, and immune cell infiltration in a xenograft animal model of transitional cell bladder carcinoma. The immune cell infiltration is of particular interest to NanOlogy for future research into the role NanoDoce may play in combination with immunoncology therapy for the treatment of advanced disease.

This work is in addition to extensive preclinical and clinical development programs underway by NanOlogy in peritoneal/ovarian cancers, prostate cancer, pancreatic cancer, pancreatic mucinous cysts, renal cell carcinoma, non-small cell lung cancer, and cutaneous metastases.

All NanOlogy investigational drugs are progressing under FDA’s streamlined 505(b)(2) regulatory pathway. The NanOlogy submicron particle technology platform is based on a patented production process that reduces the size of paclitaxel and docetaxel API crystals by up to 400 times into stable submicron particles of pure drug with exponentially increased surface area and unique geometry. The submicron particles are so unique they are protected under a composition of matter patent (US 9,814,685) valid until 2036, which provides new molecular entity-like advantages without the risks and timeline associated with NME drug development.

About NanOlogy

NanOlogy, LLC (www.nanology.us) is a private clinical stage oncology company formed in 2015 to finance and clinically develop a patented submicron particle technology platform for local, sustained delivery of proven drugs aimed at increasing their safety and efficacy in the treatment of cancer and related conditions.

Disclaimers

This announcement contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including statements about our product development, business, and other activities. Such statements are subject to the risks and uncertainties inherent in any pharmaceutical development program which may cause actual results to differ materially due to developmental, clinical trial, regulatory, market, competitive, technological, or other factors. All forward-looking statements are made as of the date of this announcement and the company disclaims any intent or obligation to update these statements. NanOlogy investigational drugs have not been proven to be safe and effective in accordance with the requirements of the U.S. FDCA and have not been approved by FDA for commercial distribution.

Contacts

Dan Eramian
Opus Biotech Communications
danieleramian@comcast.net
425-306-8716

Charles Craig
Opus Biotech Communications
charles.s.craig@gmail.com
404-245-0591

Categories
News

Wuxi AppTec: Small Molecule Chemotherapy May Play a Big Role in Cancer Immunotherapy

The combination of chemotherapies and immunotherapies highlights the significance of small molecule drug development as an ongoing treatment modality. Although there has been an explosion in immunotherapy development, small molecules continue to dominate the treatment of cancers, and recent research reveals that chemotherapies, such as taxanes, benefit immunotherapies.

The validity of combining traditional cancer chemotherapy with new immunotherapies received a major boost recently when Merck and Roche released positive findings from lung cancer clinical trials involving chemotherapy in combination with their respective checkpoint inhibitors, Keytruda (pembrolizumab) and Tecentriq (atezolizumab).

“Immunotherapy certainly represents a significant advance in cancer treatment,” says NanOlogy™ CEO Paul Dorman. “But many experts agree that combining traditional chemotherapy and immunotherapy – or chemoimmunotherapy as we call it – may benefit a greater number of patients with lung and other cancers.”

The rationale is based on recent research that has shown chemotherapy, which was once thought to be only immunosuppressive because of bone marrow suppression, is also immunogenic through its tumor killing effect. These counteracting properties partly account for why systemic administration tends to be only modestly immunogenic. Nevertheless, much oncology clinical research is in process with different combinations of chemotherapy and immunotherapy.

NanOlogy entered the emerging chemoimmunotherapy field from the chemotherapy side with unique forms of submicron particle paclitaxel, called NanoPac™, and submicron particle docetaxel, called NanoDoce™, which are designed for concentrated, sustained delivery directly to tumor sites rather than systemwide administration via intravenous infusion.

Preclinical and clinical data generated on NanoPac and NanoDoce are providing evidence that concentrated, sustained local delivery, via inhalation or intratumoral injection for example, leads to a greater tumor response without the side effects of systemically administered drug. Importantly, the investigational drugs appear to be eliciting a stronger immune response than their systemic counterparts.

As Dorman explains, “We are showing that local delivery of certain chemotherapeutic agents has the potential to improve their cancer killing properties and immunogenic effects without producing the toxic side effects of systemic administration.”

Dorman founded NanOlogy in 2015 after acquiring exclusive worldwide rights to a proprietary submicron particle production technology that could give chemotherapy renewed respect as a cancer treatment. For NSCLC, the company has developed a form of NanoPac designed for nebulized inhalation directly into the lungs.

“Lung cancer kills more people worldwide than any other cancer,” Dorman observes. “In China alone, it is responsible for more than 700,000 deaths annually. Based on our recent preclinical experience, we believe inhaled NanoPac may offer a better option than systemic chemotherapies in combination with immunotherapy for treating lung cancer.”

WuXi AppTec Communications recently talked with Dorman about the benefits of combining the new immunotherapies with traditional chemotherapies and his company’s unique approach.

WuXi: How was NanOlogy formed?

Paul Dorman:  NanOlogy was started in 2015 by DFB Pharmaceuticals, a private Texas-based investment and development company I founded in 1990 with two partners.

DFB grew through acquisitions and startups of pharmaceutical related businesses and products and ultimately sold several major operating companies in 2012 realizing significant value. We kept one of our companies, Phyton Biotech, to increase our foothold in oncology.

In addition, we increased our efforts to discover new opportunities in and around oncology. This led to the identification of an innovative submicron particle manufacturing technology developed by a company called CritiTech.

We formed NanOlogy together with CritiTech and in collaboration with US Biotest, which manages our preclinical and clinical activities. The collaboration has leveraged the unique capabilities of our three companies and has allowed us to expand the technology into multiple products and therapeutic areas.

WuXi: Why combine immunotherapies with traditional chemotherapies?

Paul Dorman: The first generation of immunotherapy drugs, such as the checkpoint inhibitors, represent a remarkable breakthrough in cancer treatment. But less than 30% of patients respond to checkpoint inhibitors and the drugs are not effective against all cancers.

When paclitaxel was introduced in the 1990s it was considered a game changer in the treatment of cancer because of how it works. The drug prevents cell division causing cell death, and its effect is much greater on rapidly dividing cells, like cancer cells, making it useful against a broad range of cancers.

The realization that chemotherapy agents like paclitaxel can have an immunogenic effect make them an attractive partner for immunotherapy. More than 170 clinical trials worldwide are in process with chemotherapy agents and checkpoint inhibitors alone to identify new and better ways to combine these agents.

Unfortunately, chemotherapy drugs do not discriminate between cancer cells and healthy cells, so systemwide administration can lead to serious systemic side effects. Additionally, these side effects are additive to toxicity of immunotherapy making it difficult to optimize their use together.

NanOlogy investigational drugs are intended to enhance tumor kill, elicit a greater immune response, and not contribute to systemic side effects – all because they are locally delivered as particles in high concentration where they become entrapped at the disease site releasing drug over a long time.

WuXi: Most chemotherapies are small molecules. With all the recent attention of academia and the news media on immunotherapies, what role will small molecules play in the future?

Paul Dorman:  Small molecules continue to dominate drug approvals and drug development in general. They constitute a broadly diverse group of therapeutic agents, and, as we have seen in treatment of cancer, they will play a key role as combination products with immunotherapeutic and other therapies.

But small molecules also have advantages over immunotherapies in that they are generally much easier to make and much less expensive to manufacture on a commercial scale. Also, advances in genomics have identified many more specific genetic targets in disease pathways that can be disrupted with small molecule drugs as well as biologics.

Our technology also provides a great example of how delivery of existing small molecules can be significantly enhanced and their therapeutic activity improved. Because paclitaxel is poorly soluble in physiologic fluids, solvents or coating agents must be added to solubilize the drug in the body, so it can be infused systemically to reach the disease site. Unfortunately, many solvents are toxic and add to the drug’s side effects.

Because of NanOlogy’s manufacturing technology, our submicron particles require no solvents or coating agents, so we can deliver pure drug particles directly to the site of the cancer, and for the first time take full advantage of the drug’s cancer killing ability, while minimizing systemic toxicity at the same time.

WuXi: Why are chemotherapy and immunotherapy synergistic when combined?

Paul Dorman: Immunotherapy checkpoint inhibitors like Keytruda, for example, are monoclonal antibodies that block a cancer cell’s ability to hide from the immune system. Once the cancer cells are exposed to the immune system, the immune system can attack and destroy them. Systemic chemotherapies are known to generate a modest immune response and that in turn stimulates the immune system to help an immunotherapy drug like Keytruda.

What we have found in our preclinical lung cancer studies is that when NanoPac is inhaled into the lungs, the local concentration and sustained release over time significantly increases tumor kill relative to systemic administration of paclitaxel. We have seen this same effect with NanoPac and NanoDoce in other tumor types as well. The enhanced kill results in greater exposure of tumor specific antigens, which elicits a stronger immune response. It stands to reason a stronger immune response will offer a greater benefit to immunotherapies.

WuXi: How is NanoPac made and how is it different from regular paclitaxel?

Paul Dorman: Intravenously administered paclitaxel is indicated for non-small cell lung cancer (NSCLC) and is one of the key agents prescribed for lung cancer. NanoPac is different because it is a novel targeted therapy made up of submicron particles of pure paclitaxel designed for nebulized inhalation. The particles of pure drug are stable in powder form without the need for coating or carrier agents.

They are formed by a proprietary manufacturing process that uses supercritical fluid carbon dioxide and sonic energy to reduce paclitaxel crystals into submicron particles without imparting static charge to the particles. So, the particles remain free flowing and stable in powder form and are simply suspended in a saline-based nebulization fluid prior to inhalation.

The particles are so unique in terms of size and shape, they have been granted a composition of matter patent in the US that is valid until 2036. Size, surface area, density, and dissolution are all protected by the patent and form our proposed regulatory specifications. This gives us new molecular entity like IP protection on NanoPac and that’s a big deal. We’ve now built an extensive patent portfolio that has been filed in China, US, Europe, Japan, and other major countries.

WuXi: What were the preclinical studies in lung cancer and what were the results?

Paul Dorman: We first did a rat inhalation pharmacokinetic study where NanoPac was successfully delivered to the lungs via nebulization without adverse effects. We found measurable amounts of drug in lung for greater than 14 days while the IV comparator, nab-paclitaxel, was gone in a couple of days. The 14-day retention of NanoPac was a surprise to the researchers performing this well-established study as they had simply never seen this length of drug retention in lung tissue.

Next, we conducted an orthotopic NSCLC study in rats where NanoPac demonstrated significantly more tumor regression and primitive tumor cell reduction than intravenously administered nab-paclitaxel. In some cases, histopathology review of the tumors showed a complete response in NanoPac-treated animals. As with the pharmacokinetic study, no adverse effects were seen with inhalation of NanoPac in this study. We presented these results at ASCO in June.

What really excited us, however, was that we saw substantial immune cell infiltration in and around dead and dying tumor tissue upon histologic exam of lung tissue. We did not see this kind of response in nab-paclitaxel or control animals.

We then conducted immunohistochemistry which showed presence of several types of cancer-killing immune cells indicating the cancer killing effect of NanoPac may result from both a drug-mediated tumor kill and an immune cell-mediated tumor kill. We’ve now seen similar immune responses with local delivery of our particles in breast, renal, and bladder tumors in animals, and prostate tumors in humans.

Our rationale for this effect is that large, sustained concentration of drug at the disease site significantly increases tumor kill and local accumulation of dead tumor cell debris. This debris exposes tumor specific antigens, which elicit a strong immune response. Because of this response and lack of systemic side effects, we believe NanoPac may be the ideal drug in combination with immunotherapy agents like Keytruda or Tecentriq for certain cancers and we are conducting further research to confirm this.

WuXi: What is your strategy for developing NanoPac in combination with immunotherapy for lung cancer?

Paul Dorman: We are advancing clinical trials in the US for local delivery of our investigational drugs in three broad therapeutic areas including gastrointestinal cancers, urological cancers, and lung cancer. We intend to progress our drugs through first-in-human clinical trials and then identify a leading oncology company to advance the products through pivotal trials, regulatory approval, and to patients in need.

For lung cancer, we think the compelling preclinical data and significant patient need require us to seek out a partner sooner. We are very interested in identifying a leading oncology company in China to help bring the product to regulatory approval in China in parallel with our efforts in the United States. We are planning to begin a formal process later this year to identify a partner in China.

WuXi: Is paclitaxel more effective in combination with immunotherapies than other forms of chemotherapy? If so, why?

Paul Dorman: Taxanes like paclitaxel and docetaxel are effective for a broad range of solid tumors and because of that we selected them as the first drugs to develop. However, what I believe is more important is the ability of our technology to place large amounts of drug at the disease site releasing drug around the clock for weeks. Contrast that with systemic administration, which only allows for drug at the disease site for a few hours with each dose, and each dose must be spaced a week or more apart.

WuXi: What other cancers are you targeting? Would you pursue combination with immunotherapy for those cancers?

Paul Dorman:  Right now, we are pursuing nine indications with our investigational drugs. In addition to our preclinical work in NSCLC, we have clinical trials underway in prostate cancer, pancreatic cancer, and pancreatic cysts via intratumoral or intracystic injection.

We also have a trial completed and another underway for peritoneal cancers, where we deliver our drug directly into the peritoneum. We also have a topical form of the product that has completed a clinical trial in actinic keratosis under another DFB company called Soria and a trial underway in cutaneous metastases.

We are planning a clinical trial in bladder cancer later this year via resected bladder tumor bed injection followed by bladder instillation and in renal cancer in 2019 via intratumoral injection.

In every case, we are seeking to deliver large, sustained amounts of drug directly to the disease site with the goal of increasing efficacy, eliciting a strong immune response, and minimizing systemic side effects. So far, the data are supporting this goal and suggest our products would benefit immunotherapy.

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NanOlogy to Unveil Positive Preclinical Data for Inhaled NanoPac® in Treatment of Lung Cancer at 2018 ASCO Annual Meeting

Update – 6/4/18:  Link to NanOlogy Poster presented at 2018 ASCO Annual Meeting

  • Studies of Inhaled NanoPac Show Prolonged Retention in the Lung, Decreased Primitive Tumor cells, and Increased Tumor Regression

FT. WORTH/DALLAS, (May 29, 2018) BUSINESS WIRE — NanOlogy LLC, a clinical-stage pharmaceutical development company, will present data from preclinical studies of inhaled NanoPac (submicron particle paclitaxel) showing prolonged retention of drug in lung tissue and significant tumor regression without adverse drug-related observations in an orthotopic animal model of non-small cell lung cancer (NSCLC).

The data will be presented in an abstract entitled “NanoPac Inhalation Treatment of NSCLC in a Nude Rat Orthotopic Lung Cancer Model” during the American Society of Clinical Oncology (ASCO) Annual Meeting on Sunday, June 3rd, from 8:00 AM to 11:30 AM in Hall A of McCormick Place in Chicago.

An initial preclinical pharmacokinetic (PK) study examined the retention of NanoPac in rat lung tissue following a single inhalation via a nose-only exposure chamber. Data showed measurable amounts of drug in the lung at the end of the 14-day study with examined tissue being microscopically indistinguishable from normal lung tissue.

A preclinical study followed to examine the therapeutic effect of inhaled NanoPac using an orthotopic model of NSCLC. Histologic analysis revealed NanoPac achieved a significant decrease in primitive tumor cell population as well as significant tumor regression.

Gere diZerega, MD, VP of Medical Affairs, said, “In our initial PK study, inhaled NanoPac resulted in longer lung retention of drug at a higher concentration compared to systemically administered paclitaxel. The evidence seen in our preclinical PK and efficacy studies has given us the confidence to move forward with IND-enabling studies in preparation for clinical trials.”

Lung cancer is by far the leading cause of cancer death according to the American Cancer Society with more than 154,000 deaths expected this year. More people die of lung cancer every year than breast, prostate, and colon cancers combined.

The preclinical lung cancer studies are in addition to an extensive clinical development program underway by NanOlogy. Local administration of NanoPac is also being evaluated in Phase 2 clinical trials for ovarian cancer (with orphan drug designation), prostate cancer, pancreatic cancer, and pancreatic mucinous cysts. A clinical trial of NanoDoce® (submicron particle docetaxel sterile suspension) is planned to begin in September for bladder cancer.

NanOlogy is also progressing a clinical trial of a submicron particle paclitaxel topical anhydrous ointment for cutaneous metastases.

All NanOlogy investigational drugs are progressing under FDA’s streamlined 505(b)(2) regulatory pathway. The NanOlogy submicron particle technology platform is based on a patented production process that reduces the size of paclitaxel and docetaxel API crystals by up to 400 times into stable submicron particles of pure drug with exponentially increased surface area and unique geometry. The submicron particles are so unique that they are protected under a composition of matter patent (US 9,814,685) valid until 2036, which provides NME-like advantages without the risk and timeline associated with new molecular entity drug development.

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About NanOlogy

NanOlogy, LLC (www.nanology.us) is a clinical stage pharmaceutical company formed by DFB Pharmaceuticals, LLC of Fort Worth, TX, CritiTech, Inc. of Lawrence, KS, and US Biotest, Inc. of San Luis Obispo, CA, to finance and clinically develop a patented submicron particle technology platform for local, sustained delivery of proven drugs aimed at increasing their safety and efficacy in the treatment of cancer and related conditions.

Disclaimer

This announcement contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including statements about our product development, business, and other activities. Such statements are subject to the risks and uncertainties inherent in any pharmaceutical development program which may cause actual results to differ materially due to developmental, clinical trial, regulatory, market, competitive, technological, or other factors. All forward-looking statements are made as of the date of this announcement and the company disclaims any intent or obligation to update these statements. NanOlogy investigational drugs have not been proven to be safe and effective in accordance with the requirements of the U.S. FDCA and have not been approved by FDA for commercial distribution.

Media Contacts

Dan Eramian
Opus Biotech Communications
danieleramian@comcast.net
425-306-8716

Charles Craig
Opus Biotech Communications
charles.s.craig@gmail.com 
404-245-0591

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New Cancer Answer

FORT WORTH, Texas—Researchers have been trying to develop therapeutic agents powerful enough to destroy tumors without harmful effects to healthy cells for a long time. NanOlogy is working toward this goal by trying to transform systemic chemotherapy into local delivery of naked nanoparticles to treat various forms of cancer with greater efficacy and safety.

DFB Pharmaceuticals is collaborating with CritiTech and US Biotest to form NanOlogy, a clinical-stage pharmaceutical development company. The objective is to finance and develop a breakthrough technology platform to produce patented, naked nanoparticle forms of paclitaxel and docetaxel for local delivery.

DFB, a private Texas investment group that develops new healthcare products and businesses—and has realized more than $1.5 billion in value through startups; strategic acquisition and sale of companies and technologies; internal product development; and brand optimization and healthcare operations—is strong in business management, according to Marc Iacobucci, managing director of NanOlogy and DFB.

CritiTech, a private Kansas particle engineering company, uses proprietary Supercritical Precipitation Technology (SCP Technology) to optimize the delivery of challenging drug substances, potent molecules and poorly soluble compounds, and to improve the efficacy, drug delivery options, dosing regimen and pharmacokinetics of wide variety of drugs, including oral, injectable and inhaled drugs. US Biotest, a private California company dedicated to developing therapeutics to address serious unmet medical needs, builds on strong relationships with industry experts, academic institutions and leading physicians to provide product development strategy and support and manage efficient delivery of programs from nonclinical through late-stage clinical trials.

As Dr. Maurie Markman, president of medicine and science at Cancer Treatment Centers of America, explained, “Systemic administration of paclitaxel and docetaxel is associated with significant adverse effects. Physicians and scientists have known for decades that paclitaxel and docetaxel are effective cancer-killing agents, and have long searched for ways to preferentially retain high concentration of drug at the treatment site to increase efficacy. The NanOlogy technology may offer a solution by enabling local delivery of large, sustained amounts of the drug at the site of disease and reducing systemic exposure and systemic side effects.”

The sterile suspension has been designed to be injected directly into tumors, cysts, peritoneum or other body cavities. Studies show that the nanoparticles remain and slowly release for four weeks, resulting in prolonged local exposure, while systemic forms of taxanes remain at the treatment site for a short time before being cleared from the body quickly.

“The nanoparticle technology platform uses sonic energy and supercritical carbon dioxide to reduce paclitaxel and docetaxel API crystals by up to 400 times into stable, naked nanoparticles with greatly increased surface area and special geometry,” explains Iacobucci. “These nanoparticles are suspended prior to use in simple vehicles without coating agents and administered in a concentrated form directly to the site of disease where they release the drug for weeks at a time.”

The company has developed sterile suspension forms of NanoPac (nanoparticle paclitaxel) and NanoDoce (nanoparticle docetaxel) as well as an inhaled form of NanoPac. A topical form called SOR007 (nanoparticle paclitaxel) ointment was developed by an affiliate, DFB Soria, and licensed to NanOlogy for clinical development in oncology.

NanOlogy’s clinical development program for NanoPac in 2017 includes clinical trial evaluation of its sterile suspension in ovarian cancer (with orphan drug designation), prostate cancer, pancreatic cancer and pancreatic mucinous cysts. The company recently announced enrollment of the first patient in a Phase 2 clinical trial of intraperitoneally administered NanoPac sterile suspension in patients with ovarian cancer, the fifth leading cause of cancer-related death in women. The trial will assess both the safety and effectiveness of NanoPac administration following surgery.

“If successful, we may add to the newer treatment options that are just becoming available and ideally improve the prognosis and quality of life for patients diagnosed with ovarian cancer,” Iacobucci said.

In addition, clinical trial evaluation of SOR007 ointment is underway for actinic keratosis (under affiliate Soria), and is expected to begin in the fourth quarter for cutaneous metastases. Clinical trials in various cancers are planned in 2018 for NanoDoce, pending approval of its IND, and the inhaled version of NanoPac is in a preclinical efficacy study for lung cancer.

November 8th, 2017
ILENE SCHNEIDER

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DFB Pharmaceuticals, CritiTech, and US Biotest Form NanOlogy™ for Clinical Development of Naked Nanoparticle Platform to Treat Cancer and Related Illnesses

September 12, 2017 05:30 AM Eastern Daylight Time

FORT WORTH, Texas–(BUSINESS WIRE)–DFB Pharmaceuticals, a private investment and development group, in collaboration with CritiTech and US Biotest, has formed NanOlogy to finance and develop a breakthrough technology platform to produce unique, patented, naked nanoparticle forms of paclitaxel and docetaxel for local delivery with the potential for greater efficacy and safety to treat cancer and other serious illnesses.

“We are excited about the potential of this technology platform to bring breakthrough therapies to patients with a wide range of cancers and other serious illnesses”Tweet this

NanOlogy has developed sterile suspension forms of NanoPac® (nanoparticle paclitaxel) and NanoDoce® (nanoparticle docetaxel) as well as an inhaled form of NanoPac. A topical form identified as SOR007 (nanoparticle paclitaxel) ointment was developed by affiliate, DFB Soria, and licensed to NanOlogy for clinical development in oncology.

The sterile suspension has been designed to be injected directly into tumors, cysts, peritoneum, or other body cavities, where studies have demonstrated the nanoparticles remain and slowly release for four weeks, resulting in prolonged local exposure. In contrast, systemic forms of taxanes remain at the treatment site for a short time as they are rapidly cleared from the body.

NanOlogy is progressing a broad clinical development program for NanoPac in 2017 that includes clinical trial evaluation of its sterile suspension in ovarian cancer (with orphan drug designation), prostate cancer, pancreatic cancer, and pancreatic mucinous cysts. In addition, clinical trial evaluation of SOR007 ointment is underway for actinic keratosis (under affiliate, Soria), and is expected to begin in the fourth quarter for cutaneous metastases. Clinical trials in various cancers are planned in 2018 for NanoDoce pending approval of its IND, and the inhaled version of NanoPac is in a preclinical efficacy study for lung cancer.

“Systemic administration of paclitaxel and docetaxel is associated with significant adverse effects. Physicians and scientists have known for decades that paclitaxel and docetaxel are effective cancer killing agents, and have long searched for ways to preferentially retain high concentration of drug at the treatment site to increase efficacy,” said Maurie Markman, MD, President of Medicine and Science, Cancer Treatment Centers of America®. “The NanOlogy technology may offer a solution by enabling local delivery of large, sustained amounts of the drug at the site of disease, and reducing systemic exposure and systemic side effects.”

NanoPac and NanoDoce are manufactured by a patented nanoparticle production technology platform that reduces the size of unprocessed paclitaxel and docetaxel crystals by up to 400 times into stable, naked nanoparticles with an exponential increase in surface area and unique geometry. Unlike other nanoparticles, which require coating agents to keep them stable, the patented NanOlogy nanoparticles are stable in their naked form and suspended prior to use in simple vehicles without coating agents.

“We are excited about the potential of this technology platform to bring breakthrough therapies to patients with a wide range of cancers and other serious illnesses,” commented H. Paul Dorman, Chairman and CEO of NanOlogy.

About NanOlogy

NanOlogy, LLC (www.nanology.us) is a company formed by DFB Pharmaceuticals, LLC of Fort Worth, TX, CritiTech, Inc. of Lawrence, KS, and US Biotest, Inc. of San Luis Obispo, CA, to finance and clinically develop a patented nanoparticle technology platform for local, sustained delivery of proven drugs aimed at increasing their safety and efficacy in the treatment of cancer and related conditions.

About DFB Pharmaceuticals

DFB Pharmaceuticals, LLC (www.dfb.com) is a private Texas investment group with an entrepreneurial drive for developing new healthcare products and businesses. Founded in 1990, DFB and its principals have realized more than $1.5 billion in value through startups, strategic acquisition and sale of companies and technologies, internal product development, brand optimization, and operations in the healthcare industry.

About CritiTech

CritiTech, Inc. (www.crititech.com) is private Kansas particle engineering company focused on developing new drugs and improving existing drugs. Using the company’s proprietary Supercritical Precipitation Technology (SCP Technology) CritiTech specializes in optimizing the delivery of challenging drug substances, potent molecules and poorly soluble compounds. In addition, CritiTech uses its SCP Technology to improve the efficacy, drug delivery options, dosing regimen and pharmacokinetics of a wide variety of drugs, including oral, injectable, and inhaled drugs.

About US Biotest

US Biotest, Inc. is a private California company dedicated to the development of therapeutics to address serious unmet medical needs. Building on strong relationships with industry experts, academic institutions, and leading physicians, the company provides product development strategy and support. US Biotest manages efficient delivery of programs from nonclinical through late-stage clinical trials.

Disclaimer

This announcement contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including statements about NanOlogy product development, business, and other activities. Such statements are subject to the risks and uncertainties inherent in any pharmaceutical development program which may cause actual results to differ materially due to developmental, clinical trial, regulatory, market, competitive, technological, or other factors. All forward-looking statements are made as of the date of this announcement. DFB disclaims any intent or obligation to update these statements. NanOlogy investigational new drugs have not been approved by FDA for commercial distribution. They have not yet been proven to be safe and effective in accordance with the requirements of the Federal Food, Drug, and Cosmetic Act.

Contacts

Opus Biotech Communications
Dan Eramian, 425-306-8716
daneramian@comcast.net
or
Charles Craig, 404-245-0591
charles.s.craig@gmail.com