On September 28, 2015 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biomedicine firm engaged in the development of effective stem cell therapies for degenerative diseases and immunotherapies for cancer, reported results from an expanded Phase I/II clinical trial evaluating the safety, feasibility and anti-tumor activity of its Chimeric Antigen Receptor-Modified T-Cells (CAR-T) immunotherapy (CBM-EGFR.1) targeting wild type EGFR (Epidermal Growth Factor Receptor) for the treatment of patients with EGFR expressing advanced relapsed/refractory solid tumors. Based on the results from 24 patients treated with CBM-EGFR (Press release, Cellular Biomedicine Group, SEP 28, 2015, View Source [SID:1234507606]).1 (17 patients with non-small cell lung cancer (NSCLC), 5 patients with cholangiocarcinoma, 1 patient with pancreatic cancer and 1 patient with renal cell carcinoma (RCC)), the early results showed that CBM-EGFR.1 immunotherapy was safe, well tolerated, and had positive signal of clinical activity in several indications. The data was selected for a late-breaking oral presentation entitled EGFR-Targeted Chimeric Antigen Receptor-Modified T Cells Immunotherapy for Patients With EGFR-Expressing Advanced or Relapsed/Refractory Solid Tumors at the 5th World Congress on Cancer Therapy in Atlanta, Georgia on September 28, 2015. The abstract can be viewed online here. The results from the first 11 NSCLC patients in the trial outlined in the abstract, entitled Chimeric Antigen Receptor-Modified T-Cells for the Immunotherapy of Patients with HER-1 Expressing Advanced Relapsed/Refractory Non-Small Cell Lung Cancer was presented at the 2015 European Cancer Congress’ (ECCO) annual meeting held in Vienna, Austria from September 25-29, 2015. The abstract can be viewed online here.

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About the Trial
The CBM-EGFR.1 phase I/II trial was designed and conducted by Chinese PLA General Hospital ("PLAGH", Beijing, also known as "301 Hospital"), led by Principal Investigator Wei Dong Han, M.D., Ph.D., head of the cancer immunotherapy department and director of molecular immunology department of the life science institute of PLAGH. The trial enrolled 24 EGFR positive (defined as at least 50% membrane staining of EGFR based on immunohistochemistry), advanced, relapsed/refractory patients with NSCLC, cholangiocarcinoma, RCC or pancreatic cancer. Most of the NSCLC patients failed EGFR-TKI therapy prior to CBM-EGFR.1 treatment. All patients provided written informed consent before enrollment, and received dose escalating infusions of CBM-EGFR.1 cells with or without conditioning chemotherapy. Autologous CBM-EGFR.1 cells were generated from 50 to 80 ml peripheral blood after a 10 to 12-day in vitro expansion, and the total CAR-expressing T cell number of 1×106/kg was set as an output control. The presence of EGFR positive cells in tumor tissues was evaluated by means of immunohistochemistry (IHC). Serum cytokines such as IL-6, IL-2, TNF-a, copy numbers of CAR-EGFR.1 transgene in peripheral blood and biopsied tissues, were monitored periodically according to assigned protocol. Clinical responses were evaluated using RECIST 1.1 and adverse events were graded by CTCAE 4.0. This study is registered with the U.S. National Institute of Health (NIH) here.

Highlight of Phase I/II clinical trial for CBMG CAR-T products in multiple advanced, refractory/relapsing solid tumors

First known report of positive safety and signal of clinical activity of EGFR CAR-T in multiple solid tumor indications
Most NSCLC patients treated with CBM-EGFR.1 failed EGFR-TKI therapy prior to CBM-EGFR.1 treatment
Overall disease control rate (DCR) is 79% (19 of 24). 100% DCR in cholangiocarcinoma (5/5), 71% DCR in NSCLC (12/17)
Objective response rate (ORR) of 25% in combined indications: 2 complete response (CR) and 1 partial response (PR) in cholangiocarcinoma, 2 PR in NSCLC and 1 PR in pancreatic cancer

The clinical responses were evaluated with RECIST1.1 and immune-related response criteria by a team of experts, and adverse events were graded with CTCAE 4.0. Of the 24 patients with evaluable clinical outcome, the overall DCR was 79% (19 of 24). Under standard protocol, an independent review of the clinical data by a separate team of experts will commence at the end of the trial. Of the 5 cholangiocarcinoma patients reported here, 2 achieved CR, 1 achieved PR, and 2 had stable disease (SD). The single pancreatic cancer patient had a PR and a single RCC patient achieved SD. Of the 17 NSCLC patients treated, 2 had PR, 10 had SD, and 5 had progressive disease. Of the 26 adverse events experienced by patients, only 1 was grade 3-4 where the patient experienced serum lipase increase. No patients experienced drug related deaths. Grade 1-2 pruritus was the most frequent adverse event experienced by patients (9/26; 35%). Desquamation and constipation are the other two frequently observed adverse events in the trial (4/26 each; 15%). Only 3 out of 24 patients exhibited Grade 2 cytokine release syndrome within one week post infusions. The median dose of transfused CBM-EGFR.1 cells was 1.18×107 cells/kg (IQR, 0.76 to 1.43×107 cells/kg). The transgene copies measured by PCR in both blood and biopsy tissues post CBM-EGFR.1 infusions indicated the trafficking of CART cells into the tumor tissues. Pathological eradication of EGFR positive tumor cells after CBM-EGFR.1 treatment was observed in tumor biopsies, along with clear evidence of the CBM-EGFR.1 cells detected in tumor-infiltrating T cells in all patients with available tumor biopsies post treatment.

Yihong Yao, Ph.D., Chief Scientific Officer of the Company commented, "The early signal of clinical activity, especially those observed in patients with late stage cholangiocarcinoma, and those with late stage NSCLC that failed prior EGFR-TKI therapy, are very encouraging. To our knowledge this is the first report of positive safety and tolerability data of EGFR CAR-T in multiple solid tumor indications. We are moving forward to confirm the safety and tolerability profile of CBM-EGFR.1 in cholangiocarcinoma and NSCLC, and will actively explore the opportunities in other solid tumor indications by implementing state-of-the-art translational medicine strategy in the clinical development. We are determined to look for early possibilities of conducting multi-center Phase IIb trials to validate the clinical activity from early observations. We have also begun to evaluate potential partners to develop an immunohistochemistry based diagnostic assay to aid in the patient selection whenever needed. We are optimistic that CBM-EGFR.1 will be able to provide late stage cancer patients with another option to extend their lives."

The Company also previously announced positive clinical data results for its Phase I clinical trials for CBM-CD19.1, CBM-CD20.1 and CBM-CD30.1 CAR-T assets targeting late-stage hematological cancer. Clinical trial data for all three constructs can be found registered with the U.S. National Institute of Health (NIH) here: NCT01864889, NCT01735604, NCT02259556.

"We are extremely excited by the recent developments resulting from the collaboration between CBMG and PLA General Hospital. These two reports on CBM-EGFR.1 therapy for late stage solid tumors have clearly demonstrated our ability to innovate, advance boundaries between basic research and translational medicine and streamline the manufacture of CAR-T and clinical treatment. We are confident and determined to be at the forefront of clinical development of these breakthrough CAR-T therapies for late stage cancer patients with solid tumors," concluded Dr. William (Wei) Cao, Chief Executive Officer of Cellular Biomedicine Group.

On September 28, 2015 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biomedicine firm engaged in the development of effective stem cell therapies for degenerative diseases and immunotherapies for cancer, reported that it responded to inquiries from investors and the scientific community about its Immuno-Oncology cell therapy platform as it relates to information surrounding CD19, CD20 and CD30 (Press release, Cellular Biomedicine Group, SEP 28, 2015, View Source [SID:1234507605]).

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Dr. William (Wei) Cao, Chief Executive Officer of Cellular Biomedicine Group commented, "We are taking a proactive approach to addressing inquiries from the investment and scientific community on the Company’s Immuno-Oncology cell therapy platform on a more real-time basis. This area has been well followed and we would like to take this opportunity to expand on frequently asked questions and dispel misinformation in the marketplace. We will continue to keep our stakeholders apprised of ongoing business and pipeline developments."

Can CBMG clarify what constructs were a part of the acquisition from PLA General Hospital’s ("PLAGH") Chimeric Antigen Receptor T cell (CAR-T) therapy and was CART-33 a part of this acquisition?
As the Company had previously announced on February 9, 2015, the recombinant expression vectors CD-19, CD-20, CD-30 and Human Epidermal Growth Factor Receptor’s (EGFR or HER1) were the only constructs acquired in addition to its respective patent applications and Phase I clinical data. At no time has CBMG acquired CART-33, which is a classification of which the Company is unaware. Details related to the acquisition and the respective constructs can be found in the Company’s Form 8-Ks filed February 9, 2015, March 25, 2015, May 26, 2015; the Form 10-K filed March 31, 2015; and the Form 10-Qs filed on May 15 and August 13, 2015. Any statement made otherwise is simply false.

In order for the community to better benchmark CBMG’s data relative to its competitors, can the Company clarify CBMG’s lead drug as it relates to patients enrolled with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL) and the respective indications of each construct?

Different from other clinical trials that have been published, CBMG’s lead drug candidate is CD-20 CART and not CD-19 CART for DLBCL. At this time we would like to reiterate that the clinical trial data presented for CD-19 CART was for B-cell Lineage Acute Lymphoblastic Leukemia (B-cell ALL); CD20 CART was for Advanced Diffuse Large B Cell Lymphoma (DLBCL) and CD30 CART was for Hodgkin’s lymphoma. It is important to note here that comparing clinical outcomes from two different drugs that target two different tumor antigens could be misleading if the detailed background of the trials are not provided. Clinical trial data for all three constructs can be found registered with the U.S. National Institute of Health (NIH) at the following links: NCT01864889, NCT01735604, NCT02259556.

What is the accurate overall response rate (ORR) for CD-19 CART?
As we had previously announced on March 25, 2015, nine adult patients with relapsed or chemotherapy-refractory B-cell lineage acute lymphoblastic leukemia (B-ALL) were enrolled in this CAR-CD19 T cell therapy trial. Different from other competitive trials, pediatric patients were not enrolled as part of this trial. Results showed a complete response (CR) rate of 22.2% (two out of nine patients) and a partial response (PR) rate of 44.4% (four out of nine patients) for an overall response rate (ORR) of 66.7% (six out of nine patients). Further subgroup analysis showed an overall response rate (ORR) of 71.4% (five out of seven patients) in the six CD-19 patients with extramedullary involvement and one patient with no extramedullary lesions and treated with autologous CAR-CD19 T cell therapy. In the six CD19 patients with extramedullary leukemia involvement or bulky adenopathy, an overall response rate (ORR) of 66.7% (four out of six patients) was achieved. It should be noted that 2 out of the 9 patients were infused with allogeneic CD-19 CART. When comparing clinical trial results that were carried out with autologous CART only, the patients infused with allogeneic CART should be excluded to allow meaningful comparison.

Can the Company clarify the overall response rate (ORR) for its CD-20 CART and CD-30 CART?
As the Company had previously reported on March 25, 2015, the results for CAR-CD20 T cell therapy trial showed an overall response rate (ORR) of 83% with five of six patients with evaluable clinical efficacy achieving complete response (CR) or partial response (PR). The Company had also previously reported on May 22, 2015, the results for CAR-CD30 T cell therapy trial showed overall response rate (ORR) of 71% with five of seven patients achieving CR or partial response PR.

Can the Company explain which vector was used in the genetic modification of patients’ T cells with anti-CD19 CAR and anti-CD20 CAR?
The transduction method utilized in the genetic modification of patients’ T cells is in fact the lentiviral vector transduction method. The Company made an error in the filing with clinicaltrials.gov and will rectify the situation immediately.

What is the next major clinical milestone for CBMG?
The Company will present CAR-T Phase I/II clinical trial data for Non Small Cell Lung Cancer (NSCLC) and Cholangiocarcinoma (CC or CCA) at the 5th World Congress on Cancer Therapy on September 28 in Atlanta, Georgia.

On September 28, 2015 Cellectar Biosciences, Inc. (NASDAQ:CLRB) ("Cellectar") reported the pricing of a registered direct offering of 1,017,272 shares of its common stock and Series B pre-funded warrants to purchase 482,728 shares of common stock at a price of $2.20 per share (Filing, 8-K, Cellectar Biosciences, SEP 28, 2015, View Source [SID:1234507596]).

Concurrently in a private placement, Cellectar is issuing Series A warrants to purchase 1,500,000 shares of common stock at an exercise price of $2.83 per share, which are not exercisable for six months from issuance and are exercisable for five years thereafter. Pursuant to a registration rights agreement, the Company has agreed to file a registration statement for the resale of the shares of common stock issuable upon exercise the Series A Warrants.

Gross proceeds from this offering are expected to be approximately $3,300,000, before deducting the estimated offering expenses payable by the company. The offering is expected to close on or about September 30, 2015, subject to customary closing conditions.

Ladenburg Thalmann & Co., Inc., a subsidiary of Ladenburg Thalmann Financial Services Inc. (NYSE MKT: LTS), acted as the exclusive placement agent for the offering.

Cellectar expects to use the net proceeds of the offering to support the Phase I clinical trial of CLR 131 for the potential treatment and management of multiple myeloma, as well as the continued development of targeted therapeutic cancer agents using the company’s proprietary phospholipid drug conjugate (PDC) delivery platform. The proceeds will also be applied to working capital, general corporate purposes and business development applications.

The shares, the pre-funded warrants and the shares issuable upon the exercise of such warrants described above are being offered by Cellectar pursuant to a shelf registration statement (File No. 333-201429) previously filed with and subsequently declared effective by the Securities and Exchange Commission ("SEC"). A prospectus supplement relating to the offering will be filed with the SEC and will be available on the SEC’s website at View Source

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Copies of the preliminary prospectus supplement and accompanying base prospectus relating to this offering may be obtained from Ladenburg Thalmann & Co., Inc., 570 Lexington Avenue, 11th Fl., New York, NY 10022, (212) 409-2000 or by accessing the SEC’s website, www.sec.gov or by emailing Cellectar Biosciences, Inc. via [email protected].

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On September 28, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the commercial availability in countries that accept the CE mark1 of the cobas EGFR Mutation Test v2, the first oncology assay from Roche that utilises either plasma or tumour tissue as a sample (Press release, Hoffmann-La Roche , SEP 28, 2015, View Source [SID:1234507594]). The test identifies 42 mutations in the epidermal growth factor receptor (EGFR) gene, the most of any In-vitro Diagnostic (IVD) on the market, and can also be used as an aid in selecting eligible patients with non-small cell lung cancer (NSCLC) for therapy with an EGFR tyrosine kinase inhibitor (TKI).

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"As more targeted therapies become available, it is critical that we provide innovative molecular testing methods that make it easier for patients to get tested, regardless of the surgery risks or tumour tissue availability," said Roland Diggelmann, COO, Roche Diagnostics. "By investing in liquid biopsy research and developing the cobas EGFR Mutation Test v2 for use with either plasma or tissue samples, Roche is helping to remove these common barriers from molecular testing."

According to a recent survey of more than 550 oncologists, EGFR genetic testing is not being conducted in about 25 percent of patients with NSCLC2,3. Some of the reasons for not testing included lack of diagnostic material and cases where a patient was deemed unfit to undergo biopsy. With the cobas EGFR Mutation Test v2 being validated with both tissue and plasma sample types, patients who previously did not qualify for biopsy now have the opportunity to receive a result from a simple plasma test to guide the corresponding therapy.

The cobas EGFR Mutation Test v2 is available now in countries that accept the CE mark1. For more information, please visit www.cobas-egfrtestv2.com.

About the cobas EGFR Mutation Test v2
The cobas EGFR Mutation Test v2 is a real-time PCR test that identifies 42 mutations in exons 18-21, including L858R, exon 19 deletions, L861Q and the TKI-resistance mutation, T790M. It is designed to enable testing of either tissue or plasma specimens with one kit, and allows labs to mix-batch tissue and plasma on the same plate. Additionally, Roche has developed a cell-free DNA (cfDNA) sample preparation kit that is optimised for extracting the DNA from plasma.

When testing plasma with the cobas EGFR Mutation Test v2, a new feature called the Semi-Quantitative Index (SQI) is included in the report. This number is designed to reflect a trend in the amount of mutant cfDNA in the sample. When frequently testing for the EGFR mutation using the test, tracking the SQI value and identifying a trend may lead to understanding tumour progression.
The cobas EGFR Mutation Test v2 is designed to run on the cobas 4800 System, v2.1 or higher. The system can also be used for the detection of mutations in the KRAS and BRAF gene of tumour samples.

On September 28, 2015 Rexahn Pharmaceuticals, Inc. (NYSE MKT: RNN), a clinical stage biopharmaceutical company developing next generation therapeutics for the treatment of cancer, reported that preliminary clinical data from ongoing Phase I studies of its anti-cancer compounds, Supinoxin and RX-3117, were presented on Sunday, September 27, 2015 in two poster presentations at the joint 18th ECCO – 40th ESMO (Free ESMO Whitepaper) European Cancer Congress 2015 – a biennial congress focused on improving the prevention, diagnosis, treatment and care of cancer patients, taking place in Vienna, Austria, September 25-29, 2015 (Filing, 8-K, Rexahn, SEP 28, 2015, View Source [SID:1234507591]).

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"We were pleased to have the opportunity to showcase promising preliminary data from both the Supinoxin and RX-3117 clinical programs at this prestigious cancer meeting," commented Dr. Peter D. Suzdak, Chief Executive Officer of Rexahn Pharmaceuticals. "The initial clinical results demonstrate that both Supinoxin and RX-3117 appear to be safe and well tolerated and also show encouraging preliminary evidence of clinical activity. We believe these results underscore the unique mechanism of action of both compounds and their ability to selectively target key molecular pathways involved in cancer biology."

Supinoxin Clinical Program

Preliminary results from the Phase I Supinoxin clinical trial were presented on September 27, 2015 by study investigator, Dr. Gail Eckhardt, Professor of Medicine/Oncology at the University of Colorado Cancer Center, in a poster presentation entitled "Single Agent Supinoxin Targeting Phosphorylated p-68 Preliminary Phase I Data."

The results demonstrated that, at the dose levels tested to date, Supinoxin administered orally appeared to be safe and well tolerated with no Grade 3 or Grade 4 adverse events and only one unrelated Grade 2 adverse event. The most frequently reported drug related adverse events were mild nausea, vomiting and fatigue. Pharmacokinetic analyses of the current data demonstrate both a predictable and desirable pharmacokinetic profile for an orally-administered route of therapy.

Clinical evidence of single-agent activity of Supinoxin was also observed in 4 patients who showed stable disease persisting from between 255 and 497 days as of September 14, 2015. Currently, 3 of the 4 patients exhibiting stable disease remain on active treatment and continue to be followed in the study.

"Supinoxin’s novel mechanism of action targets a new biological pathway that is involved in the proliferation and metastasis of numerous types of cancers," said Dr. Eckhardt. "We are very excited about the novelty of this approach and the potential for Supinoxin to treat historically difficult-to-treat cancers, such as triple negative breast cancer, for which there is a tremendous unmet medical need."

Dr. Ely Benaim, Chief Medical Officer of Rexahn Pharmaceuticals, remarked "We are very encouraged by the emerging data from the Phase I study, which demonstrate that Supinoxin can be administered safely to cancer patients with advanced disease and appears to have a pharmacokinetic profile suggesting its utility as an orally administered, novel targeted therapy to treat cancer patients. Moreover, the observation of stable disease for relatively prolonged periods of time in certain patients is particularly encouraging and certainly warrants further clinical investigation. We look forward to determining the maximum tolerated dosein the current study and then using that dose to treat selected patient populations in Phase Ib/IIa clinical proof-of-concept studies with Supinoxin next year."

Supinoxin is a first-in-class, orally bioavailable, small molecule inhibitor of a cancer protein (phosphorylated p-68) believed to play a prominent role in cancer cell development and proliferation. Supinoxin is currently being evaluated in an ongoing Phase I multi-center, dose-finding, open-label, single agent clinical study in patients with advanced or metastatic solid tumors. Patients in the study were treated once weekly for 3 weeks, with 1 week off treatment, comprising a 28-day treatment cycle.

The Phase I clinical study is designed to evaluate the safety, tolerability, dose-limiting toxicities, and maximum tolerated dose (MTD) of Supinoxin and identify a recommended phase Ib/IIa dose and dosing schedule for continued clinical development. Secondary endpoints in the study include pharmacokinetics and anti-tumor activity.

Based on the favorable safety and pharmacokinetic profile seen at the highest dose levels (575 mg and 775 mg), Rexahn has initiated a dosing schedule modification to increase patients’ daily exposure of Supinoxin. All newly enrolled patients are now receiving Supinoxin either three or five times weekly as opposed to once weekly. The new dosing paradigm will increase drug exposure, maximizing potential therapeutic activity and enable more rapid determination of the MTD for further clinical study.

RX-3117 Clinical Program

In a second poster presentation entitled, "Preliminary Phase I Data of Single Agent RX-3117, an Oral Antimetabolite Nucleoside," Dr. Drew W. Rasco, Clinical Investigator at South Texas Accelerated Research Therapeutics, presented preliminary clinical findings from an ongoing Phase Ib clinical trial of RX-3117.

In the Phase Ib multi-center, dose escalation, open-label clinical trial of RX-3117, patients with advanced and metastatic solid tumors were treated 3 times per week for 3 weeks, with 1 week off of treatment, comprising a 28-day treatment cycle. The primary objectives of the study were to characterize the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of RX-3117, and to determine a maximum tolerated dose and dosing schedule for further clinical development in Phase Ib/IIa clinical studies.

Preliminary results from the ongoing Phase Ib clinical trial presented at the conference demonstrate that – at the doses tested to date, RX-3117, administered orally, appeared to be safe and well tolerated with a predictable pharmacokinetic profile. The most frequently reported treatment emergent adverse events were mild to moderate fatigue, gastrointestinal disturbances, anemia, pyrexia, decreased appetite and dehydration.

In addition, preliminary anti-tumor activity was seen in the Phase Ib clinical trial, with evidence of tumor reduction observed in 1 patient and stable disease observed in 5 patients persisting from between 112 and 276 days before disease progression occurred.

"It is certainly encouraging that at this early stage there is some preliminary evidence of anti-tumor activity in patients with relapsed, refractory tumors. Based on the accumulating preclinical and clinical data, RX-3117 could hold promise in the treatment of gemcitabine-resistant cancers. This type of targeted, next generation chemotherapy, that can potentially be given orally with less systemic toxicity, could advance the treatment paradigm for cancer, improving outcomes and quality of life for patients," remarked Dr. Rasco.

"While these are early-stage trials, which should be interpreted with caution, we are very encouraged by the excellent tolerability profile and preliminary evidence of clinical activity and disease control observed in the ongoing clinical studies. We are excited about the interest in our programs within the oncology community and look forward to continuing the clinical development of Supinoxin and RX-3117 in Phase Ib/IIa clinical proof-of-concept studies," said Dr. Benaim.

RX-3117 is a novel, orally bioavailable small molecule, investigational anti-cancer therapy that targets a unique biological pathway implicated in the development and metastasis of numerous cancers. Preclinical studies of RX-3117 in patient-derived, cancer cell xenograft models have demonstrated broad anti-tumor activity of RX-3117 and, most importantly, an ability to treat cancer cells that have become resistant to gemcitabine – a widely-used chemotherapy. Unfortunately, resistance to gemcitabine occurs in a significant number of patients over time, reducing overall treatment efficacy and further limiting options for patients.

Based on the favorable safety and pharmacokinetic profile seen at the highest dose levels (1,500 mg and 2,000 mg) Rexahn has initiated a dosing schedule modification to increase patients’ daily exposure of RX-3117. All newly enrolled patients are now receiving RX-3117 either five or seven times weekly as opposed to three times weekly. The new dosing paradigm will increase drug exposure, maximizing potential therapeutic activity and enable more rapid determination of the MTD for further clinical study.

About Supinoxin (RX-5902)
Supinoxin (RX-5902) is an orally administered, potential first-in-class, small molecule inhibitor of phosphorylated-p68 (P-p68). P-p68, which is selectively overexpressed in cancer cells and is absent in normal tissue, increases the activity of multiple cancer related genes including cyclin D1, c-jun and c-myc, and plays a role in tumor progression and metastasis. Over-expression of phosphorylated-p68 has been observed in solid tumors, such as melanoma, colon, ovarian and lung tumors. In preclinical studies, Supinoxin has been shown to inhibit proliferation of cells in over 100 different human cancer cell lines, including breast, colon, pancreas, ovarian, and stomach cancers, and showed potent activity in drug-resistant cancer cells. In preclinical animal models, where human cancer cells from melanoma, pancreas, renal or ovarian tumors were grafted into animals, treatment with Supinoxin resulted in a significant reduction in tumor growth.

Supinoxin is currently being evaluated in a Phase I dose-escalation clinical trial in cancer patients with solid tumors designed to evaluate the safety, tolerability, dose-limiting toxicities and maximum tolerated dose (MTD). Secondary endpoints include pharmacokinetic analysis and an evaluation of the preliminary anti-tumor effects of Supinoxin. This trial is being conducted at three clinical oncology centers in the United States. Each patient has the ability to continue on the drug for up to six cycles of treatment (a dosing cycle is defined as three weeks of drug treatment followed by one week off) if no disease progression is seen. Patients are assessed by CT or MRI prior to the start of therapy and after every two cycles of therapy to assess tumor progression. The decision to escalate dose is made after completion of one cycle of treatment based on safety and tolerability. Patients may receive up to six cycles of treatment if their disease does not progress. Tumor biopsy samples are taken to assess the biomarker phosphorylated-p68. Patients in nine dose groups (25, 50, 100, 150, 225, 300, 425, 575, and 775 mg) have been enrolled to date, and at this time, the MTD has not yet been reached. Given the robust preliminary safety profile observed in the Phase I clinical trial to date, it is difficult to predict when the MTD will be achieved and the trial will be completed.

About RX-3117
RX-3117 is a novel, investigational small molecule nucleoside compound. Once intracellularly activated (phosphorylated) by UCK2, it is incorporated into the DNA or RNA of cells and inhibits both DNA and RNA synthesis, which induces apoptotic cell death of tumor cells. UCK2 is overexpressed in various human cancer cells. Preclinical studies have shown that RX-3117 inhibits the growth of various human cancer xenograft models, including pancreatic, lung, bladder, cervical and colon, as well as gemcitabine resistant cancer cells.

RX-3117 has demonstrated broad spectrum anti-tumor activity against over 100 different human cancer cell lines and efficacy in 17 different mouse xenograft models. Notably, the efficacy of RX-3117 in the mouse xenograft models was superior to that of gemcitabine. Further, RX-3117 still retains its full anti-tumor activity in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine. In August 2012, Rexahn reported the completion of an exploratory Phase I clinical trial of RX-3117 in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of a 50 mg dose of RX-3117 demonstrated an oral bioavailability of 56% and a plasma half-life (T1/2) of 14 hours. In addition, RX-3117 appeared to be safe and well tolerated in all subjects throughout the dose range tested.

RX-3117 is currently being evaluated in a Phase Ib clinical trial in cancer patients with solid tumors. The Phase Ib clinical trial is a multi-center, dose-escalation study that will evaluate the safety, tolerability, dose-limiting toxicities, and maximum tolerated dose (MTD) of RX-3117 in patients with solid tumors. Secondary endpoints include pharmacokinetic analysis, and an evaluation of the preliminary anti-tumor effects of RX-3117. Patient enrollment has been completed in nine dose groups (30, 60, 100, 150, 200, 500, 1000, 1500 and 2000 mg). The MTD of RX-3117 has not yet been achieved. Given the robust preliminary safety profile observed in the Phase Ib clinical trial to date, it is difficult to predict when the MTD will be achieved and the trial will be completed.