On November 17, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported the presentation of both clinical and nonclinical data for Ad-RTS-hIL-12 + orally-administered veledimex for recurrent brain cancer at the 21st Annual Scientific Meeting of the Society for Neuro-Oncology (SNO) held November 17-20, 2016 in Scottsdale, Arizona (Press release, Ziopharm, NOV 17, 2016, View Source [SID1234516675]). Ad-RTS-hIL-12 + veledimex is a novel viral gene therapy candidate utilizing the proprietary RheoSwitch Therapeutic System (RTS) technology for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating a vigorous immune response against cancers.

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In a poster presentation titled "Phase 1 study of intra-tumoral viral delivery of Ad-RTS-hIL-12 + oral veledimex is well tolerated and suggests survival benefit in recurrent high-grade glioma," the Company will report interim results from patients with recurrent high-grade gliomas enrolled in three veledimex dosing cohorts (20mg, n=7; 30mg, n=4; and 40mg, n=6). Subjects with relapsed high-grade gliomas, either glioblastoma (GBM) or anaplastic astrocytoma (AA), undergoing re-resection were intra-tumorally injected once with Ad-RTS-hIL-12 along with oral doses of veledimex to activate and control production of IL-12.

As of October 14, 2016, the date of data collection for the SNO presentation, median overall survival (mOS) was 12.8 months, with 11 of 17 subjects alive. Survival rates at 6, 9, and 12 months for patients with multiple recurrences prior to administration of Ad-RTS-hIL-12 are described in the table:

Treatment N Relapsed Brain Tumor Medium #
Recurrences mOS (months) Survival Rate (%)
6 months 9 months 12 months
Ad + V (Overall) 17 16 GBM, 1 AA 3 12.8 87 65 54
Ad + V (20 mg) 7 6 GBM, 1 AA 3 12.8 100 86 71
GBM is an aggressive brain tumor affecting approximately 74,000 people worldwide each year.i,ii For patients who have experienced recurrences the prognosis is particularly poor, with a mOS of 6-7 months, while mOS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iii, iv

In the study, IL-12 leading to the production of interferon-gamma in the bloodstream was measured and found to be proportional to the three doses of veledimex, demonstrating that this orally-delivered activator crossed the blood brain barrier to engage the RTS gene switch and express IL-12 in a dose-dependent manner. Toxicities in all three dose cohorts were consistent with those previously reported, with a higher incidence of grade 3 or greater adverse events in the 40 mg dose group. Importantly, all related side effects were reversed upon cessation of veledimex. Based on the tolerability and survival benefit seen, the 20 mg dose of veledimex has been selected for an ongoing expansion cohort.

"These translational data confirm the activity of Ad-RTS-hIL-12 + veledimex in the clinic, demonstrating that veledimex crosses the blood brain barrier to activate the RheoSwitch gene switch and produce IL-12, resulting in an immune response to the tumor and now, impressively, overall survival outcomes," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "With median overall survival beyond 12 months in these patients who have experienced multiple recurrences, the therapeutic potential of Ad-RTS-hIL-12 + veledimex is very promising. We look forward to enrolling additional patients in the expanded 20 mg dose cohort and to discussing the results of the Phase I multi-center study with the FDA, with the goal of determining a registration pathway for this therapeutic in a disease with far too few treatment options."

The Company will also present results from a pre-clinical study of Ad-RTS-mIL-12 + veledimex as an investigational therapy for pediatric glioma in a poster titled "Local regulated IL-12 expression as an immunotherapy for the treatment of pontine glioma". Glioma in the pontine region of the brain accounts for approximately 15% of all cases of pediatric brain tumors, with a median survival time of less than one year. In an orthotopic pons model, veledimex was shown to cross the blood brain barrier to control mouse IL-12 production from the tumor, which stimulated the immune system and resulted in a profound increase in overall survival. Based on these results, the Company plans to initiate a Phase 1 clinical trial in pediatric brain tumors, including diffuse intrinsic pontine glioma (DIPG) in 2017.

"DIPG is an aggressive disease, and because of its location in the brain, it is virtually untreatable," added Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "Ad-RTS-hIL-12 + veledimex has unique potential in this indication especially given our ability to not only turn IL-12 on and off, but also to titrate IL-12 levels thanks to the RTS technology. Our Ad-RTS-IL-12 + veledimex program continues to gain momentum, with the potential for a registration pathway in recurrent high-grade glioma in adults and expected study initiations as monotherapy in pediatric patients, as well as, in combination with checkpoint inhibitors in adult patients with brain cancer."

All poster presentations will be available online at www.ziopharm.com.

On November 17, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused, clinical stage biotechnology company, reported that following the successful conjugation of multiple, natural product cytotoxic molecules developed by Pierre Fabre to Cellectar’s PDC delivery platform, it has initiated in vivo studies for a variety of solid tumors (Filing, 8-K, Cellectar Biosciences, NOV 17, 2016, View Source [SID1234516674]).

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Harnessing a selection of linkers to attach the cytotoxic molecules to the PDC platform, the company has constructed a series of novel compounds specifically designed for improved tumor targeting. This research collaboration falls under the company’s CLR CTX programs, geared to convert non-targeted cytotoxic agents into targeted cancer treatments when combined with Cellectar’s proprietary delivery system. The drug’s targeting enhancement is designed to further improve efficacy and reduce adverse events.

As part of the Pierre Fabre research collaboration, Cellectar has already completed a series of in vitro studies with the newly created compounds, and is currently compiling early efficacy data. Cellectar will then initiate additional in vitro and in vivo studies in melanoma, lung, and colon cancers, as well as in additional solid tumors.

"We are pleased with the advancement of these programs and look forward to sharing data from our development work with Pierre Fabre," said Jim Caruso, president and CEO of Cellectar Biosciences. "This partnership continues to create value for both of our companies. In parallel, we continue to make significant progress on our lead radiotherapeutic PDC, CLR 131, for the treatment of relapsed/refractory multiple myeloma, including our ongoing Phase I and our impending NCI-supported Phase II clinical trial in selected hematologic malignancies."

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first quarter of 2017. Based upon preclinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall response rate (ORR), an improvement in progression-free survival (PFS) and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Relapsed or Refractory Multiple Myeloma
Multiple myeloma is the second most common blood or hematologic cancer with approximately 30,000 new cases in the United States every year. It affects a specific type of blood cells known as plasma cells. Plasma cells are white blood cells that produce antibodies to help fight infections. While treatable for a time, multiple myeloma is incurable and almost all patients will relapse or the cancer will become resistant/refractory to current therapies.

On November 17, 2016 Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a preclinical and clinical-stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported it has received verbal positive guidance from the FDA regarding its planned IND submission indicating that the Company may incorporate by reference the IND established by a prior developer (Press release, Moleculin, NOV 17, 2016, View Source [SID1234516671]).

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Moleculin’s Chairman and CEO, Walter Klemp, commented, "This new positive guidance removes a major question mark and allows us to create a tighter timeline for the estimated beginning of our next clinical trial. To be clear, we still can’t rule out the possibility of a delay in the timeline, but with the knowledge that the FDA is encouraging us to simply incorporate by reference the prior developer’s IND, we believe we can accelerate our IND submission process. On our current path, we expect to be able to file our IND submission before year end. Barring a negative surprise from the FDA’s review of our submission, that should allow us to begin treating patients in our next clinical trial several months sooner than expected."

The Company has indicated in previous disclosures that it expected to begin its next clinical trial by the first half of 2017, however this development may reduce that time frame by several months. The Company has submitted a pre-IND briefing document to the FDA along with key questions regarding its clinical development plan and a request for a meeting, if the FDA deems it necessary. The FDA recently indicated in writing that it intends to provide written responses to the Company by December 6, 2016 and that it does not believe a live meeting is necessary. Once those written responses are received, the Company will adjust its final IND submission document accordingly and submit for final FDA review. IND submissions are normally reviewed within 30 days of filing.
The beginning of the Company’s next clinical trial for Annamycin will depend on many things, including but not limited to the absence of any objections by the FDA to the Company’s IND submission, review and approval by an appropriate Institutional Review Board (IRB) representing the proposed clinical site or sites, and the ultimate recruitment of patients by qualified clinical testing sites.

Dr. Don Picker, Moleculin’s COO added, "Based on this positive guidance, we have already begun discussions with suitable testing sites so that we can begin recruiting as soon as we have IRB approval. We intend to hit the ground running as soon as the IND is active."