On December 4, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the initiation of Cohort 6 of its ongoing Phase 1b trial evaluating CLR 131 for the treatment of relapsed/refractory (R/R) multiple myeloma (MM) (Press release, Cellectar Biosciences, DEC 4, 2018, View Source [SID1234531899]). Cohort 6 will evaluate up to four patients with each receiving two doses of 18.75 mCi/m2 of CLR 131 administered one week apart. This fractionated dosing regimen will result in each patient being treated with a total of approximately 75.0 mCi of CLR 131, representing an increase in average total exposure of greater than 15% over Cohort 5.

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Cohort 5 also used a fractionated dosing regimen and results showed an ability to administer higher average drug exposure compared with previous cohorts that used bolus dosing. The results seen in Cohort 5 suggest the potential of fractionated dosing to reduce adverse events while improving efficacy. The independent Data Monitoring Committee (DMC) determined the Cohort 5 dose to be safe and well tolerated, and the DMC recommended advancement to the higher dose being used in Cohort 6.

"Cohort 6 builds upon the fractionated dosing we successfully employed with Cohort 5, and we look forward to the results from utilizing a higher drug concentration in this two-dose fractionated approach," said James Caruso, president and chief executive officer of Cellectar Biosciences. "Importantly," Caruso continued, "while cohort 5 showed fewer adverse events than cohort 4, total radiation exposure was greater."

Cohort 5 Results

Results from Cohort 5 indicated enhanced tolerability and safety compared with Cohort 4 despite an 18% increase in total average dose, from 55.29 mCi in Cohort 4 to 65.15 mCi in Cohort 5. Patients in Cohort 5 required less supportive care such as transfusions of platelets or packed red blood cells than seen in previous cohorts.

In addition to the improved safety profile demonstrated in Cohort 5, the company also monitored signals of efficacy. Despite Cohort 5 patients averaging five lines of prior systemic therapies, all patients experienced clinical benefit with two patients achieving minimal responses and two achieving stable disease. Furthermore, looking at surrogate markers, patients in Cohort 5 monitored by M-protein showed a nearly 50% further reduction in M-protein than seen in Cohort 4.

Based on these results and the DMC recommendation, Cellectar plans to modify the single-dose regimen of its ongoing Phase 2 trial of R/R hematologic malignancies to fractionated dosing.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated phospholipid ether-drug conjugate (PDC) therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in relapsed/refractory multiple myeloma (R/R MM) and a range of B-cell malignancies, and a Phase 1b clinical study in patients with R/R MM exploring fractionated dosing. The objective of the multicenter, open-label, Phase 1b dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2 as well as a fractionated dose of 15.625 mCi/m2 given twice over seven days in Cohort 5. All study doses and regimens have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma as well as a second Phase 1 study in combination with external beam radiation for head and neck cancer.

About Phospholipid Drug Conjugates

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized PDCs to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

On December 4, 2018 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform, reported that Dr. Gerrit Dispersyn, President and Chief Operating Officer, will give a presentation at the Tumor Targeted Lymphocytes Summit being held at the Hilton Boston Back Bay in Boston on December 11-13 (Press release, Phio Pharmaceuticals, DEC 4, 2018, View Source [SID1234531867]).

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Dr. Dispersyn’s presentation, titled "Therapeutic Enhancement of TILs with Self-Delivering RNAi through Targeted Gene Silencing," will take place at 12:10 p.m. ET on Thursday, December 13. He will present an overview on the use of RNAi to improve the immunobiology of tumor infiltrating lymphocytes (TILs) and other immune effector cells, how its use compares to other approaches in Adoptive Cell Therapies (ACT), and considerations for clinical and commercial applicability.

Dr. Dispersyn’s presentation will be available under the "Investors – Events and Presentations" section of the Company’s website, www.phiopharma.com, approximately one hour following the presentation.

The Tumor Targeted Lymphocytes Summit is focused on the topic of optimizing the clinical translation of TILs and endogenous T cells to improve the efficacy of ACT

On December 4, 2018 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has engaged cGMP Validation L.L.C. (cGMP Validation) to assist in the preparation of the Investigational New Drug application (IND) that must be submitted to and approved by the U.S. Food and Drug Administration (FDA) before PharmaCyte can begin its planned clinical trial in patients with locally advanced, non-metastatic, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, DEC 4, 2018, View Source [SID1234531883]).

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cGMP Validation is playing a pivotal role for PharmaCyte and will continue to do so as it moves forward with the preparation of its IND. The role of cGMP Validation and its President and Chief Executive Officer, Jesse Gillikin, in particular, is to ensure that each and every step of the manufacturing process of PharmaCyte’s encapsulated cells completely complies with the FDA’s cGMP regulations and all other FDA requirements requested by the U.S. drug regulatory agency. In addition to ensuring that PharmaCyte’s clinical trial product meets regulatory compliance throughout the production process, cGMP Validation will also serve as a resource to Austrianova in its manufacturing process related to cGMP requirements with which it must adhere. For example, cGMP Validation will examine cGMP required documents prepared by Austrianova that concern all "production runs" of the manufacturing process and work with Austrianova to ensure compliance in every respect.

cGMP Validation will also serve, on behalf of PharmaCyte, as the agent for the "release" of the final product that will be implanted into patients before the chemotherapy prodrug ifosfamide is given during the planned clinical trial in LAPC.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, commented, "We are extremely fortunate to have been able to retain cGMP Validation as our outside cGMP compliance/validation expert and to have Mr. Gillikin work directly with us and the principals at Austrianova to make certain that the very important manufacturing portion of our IND is complete and compliant with the FDA’s stringent cGMP regulations.

As I mentioned in an interview last summer, we’re almost there. Our checklist of items to be completed has been whittled down to just a few remaining items, and cGMP Validation provides us with the confidence moving forward to get across the finish line. It is imperative that our submission of the IND to the FDA is done flawlessly; therefore, cGMP Validation’s efforts will play a major role in ensuring that the IND we plan to submit to the FDA is as complete and accurate as possible."

cGMP Validation was established in 1997 as a full-service validation/compliance firm offering services for the pharmaceutical, biotechnology, biologics, medical device and medical diagnostic sectors. It has served new and repeat clients across the U.S., Puerto Rico and Canada and has international experience in Europe, Egypt, Korea, Indonesia and Vietnam. cGMP is headquartered in North Carolina, and it has an operational office in Missouri.

Mr. Gillikin is a co-founder of cGMP Validation and serves as its President and Chief Executive Officer. He has been in the pharmaceutical industry since 1978 and has experience in validation, managing QC laboratories, field auditing, and compliance, including interactions with the FDA and international regulatory agencies. His experience has included working with numerous companies in establishing validation and compliance practices. Mr. Gillikin’s experience enables him to provide clients with a wide array of validation resources, such as manufacturing equipment validation, process validation, cleaning validation and computer validation. His extensive work with other companies, as well as his long-standing relationship and experience with the FDA, also enables him to provide auditing, compliance/validation program building and the writing/execution of validation protocols.

Because of the intense efforts that PharmaCyte, cGMP Validation, and PharmaCyte’s clinical team of consultants are currently engaged in with respect to the preparation of the IND, as well as difficulty in coordinating and scheduling travel with everyone involved during the holiday season, PharmaCyte has decided to postpone its planned shareholder meeting until the first quarter of 2019.

On December 4, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported the dosing of the first patient in a Phase 2 combination trial to evaluate MedImmune’s MEDI0457 (formerly called INO-3112 which MedImmune in-licensed from Inovio) in combination with durvalumab targeting a broad array of cancers associated with the human papilloma virus (HPV) (Press release, Inovio, DEC 4, 2018, View Source [SID1234531968]).

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This open-label trial funded by MedImmune, the global biologics research and development arm of AstraZeneca, is sponsored by noted cancer researcher Dr. Michael Frumovitz, MD, MPH, of the MD Anderson Cancer Center in Houston, Texas. MedImmune is evaluating MEDI0457 in combination with durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with HPV-associated cervical, anal, penile, and vulvar cancers in arms of a clinical trial with an estimated total enrollment of 77 patients. For additional information about the study, please visit www.clinicaltrials.gov (search identifier NCT03439085).

The opening of this trial will result in a milestone payment from MedImmune to Inovio. Financial arrangements were not disclosed.

Dr. Frumovitz said, "This is the first Phase 2 clinical trial at MD Anderson that is focused not on the site of disease origin, but instead on the cause of a cancer — in this case exposure to HPV 16 or 18. The HPV Moon Shot at MD Anderson has developed an entire research program with this philosophy in mind — that HPV-associated cancers behave similarly, regardless of site of origin, and should be studied as a whole, not as individual cancers. This study will be "site agnostic", meaning any patient with an HPV 16/18 associated cancer, regardless of primary site, will be eligible. Another truly unique aspect of this study is a separate cohort for patients who are HIV positive with an HPV 16/18 associated cancer."

Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, "We are pleased to see Inovio’s cancer-fighting immunotherapy, in MEDI0457, expand to new cancer indications. Such expansion is great for patients and the oncology community. For Inovio, amplification of HPV cancer targets holds the potential to bring about additional milestone and royalty payments."

An article in the online edition of Clinical Cancer Research highlights a recent Phase 1 study of MEDI0457 as a monotherapy in 22 HPV-positive patients with HPV-associated head and neck cancer that demonstrated MEDI0457 generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood and increased CD8+ T cell infiltration in resected tumor tissue. One patient in that trial who initially displayed a slight increase in T cell immune responses developed progressive disease at 11 months into the study and subsequently received a PD-1 checkpoint inhibitor. The patient achieved a complete response, which has sustained for over two years and counting. Increasing evidence suggests that response rates from checkpoint inhibitors can be enhanced when used in combination with cancer vaccines like MEDI0457 that generate tumor-specific T cells.

About MEDI0457 and VGX-3100

MEDI0457 (formerly called INO-3112 (VGX-3100, plus IL-12) which MedImmune in-licensed from Inovio) is under evaluation by MedImmune to treat HPV-associated cancers. Inovio is investigating VGX-3100, a DNA-based immunotherapy for the treatment of HPV-16 and HPV-18 infection and pre-cancerous lesions of the cervix (Phase 3) and vulva (Phase 2) and anal (Phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for pre-cancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of pre-cancerous cells. In a randomized, double-blind, placebo-controlled Phase 2b study in 167 adult women with histologically documented HPV-16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient’s own immune system to clear HPV-16 and HPV-18 infection and pre-cancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

Under the 2015 agreement, MedImmune acquired exclusive rights to Inovio’s INO-3112, now called MEDI0457. MEDI0457 targets cancers caused by HPV types 16 and 18 which are responsible for more than 70 percent of cervical pre-cancers and cancers and are involved in the development of other tumors. Within the broader license and collaboration agreement, MedImmune and Inovio are co-developing one additional DNA-based cancer therapy product not included in Inovio’s current product pipeline, which MedImmune has exclusive rights to develop and commercialize. Inovio will receive development, regulatory and commercialization milestone payments for these additional cancer vaccine products and will be eligible to receive royalties on worldwide net sales.

About Durvalumab

Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumor’s immune-evading tactics and inducing an immune response. As part of a broad development program, durvalumab is being investigated as monotherapy and in combination with IO, small molecules, and chemotherapies across a range of tumors and stages of disease.

On December 3, 2018 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the presentation of the efficacy and safety results of oral rigosertib in combination with azacitidine (Vidaza) in patients with HR-MDS reported at an oral presentation during the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego (Press release, Onconova, DEC 3, 2018, View Source [SID1234531818]). Rigosertib, the Company’s lead compound, is being evaluated in both intravenous and oral forms.

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ORAL PRESENTATION:

Phase 2 Expansion Study of Oral Rigosertib Combined with Azacitidine treatment in Patients with Higher-Risk (HR) Myelodysplastic Syndromes (MDS): Efficacy and Safety Results in HMA Treatment Naïve & Relapsed (Rel)/Refractory (Ref) Patients

Session Name: 637. Myelodysplastic Syndromes — Clinical Studies: Novel Therapeutics I

Date: Saturday, December 1, 2018

Presentation Time: 4:15 PM PST

Seventy-four (74) patients were treated with a median age of 69 years (range 42-90) at 9 clinical sites, and received either 840 mg or 1,120 mg of oral rigosertib daily divided into two doses, in combination with a standard dose of injectable azacitidine. Of the 55 evaluable patients, 29 patients were treated with a daily dose of 1,120 mg of oral rigosertib, either 560 mg twice daily (12 patients) or 840 mg in the a.m. and 280 mg in the afternoon (17 patients). Twenty-six patients were treated with 560 mg in the AM and 280 mg in the PM (daily dose of 840 mg) for the first three weeks of a four-week cycle. All patients also received 75 mg/m2/day SC or IV azacitidine during the second week of the four-week cycle. The median duration of treatment for the HMA naïve and HMA failed patients was 7.8 and 4.9 months respectively. The median duration of response in these groups was 12.2 and 10.8 months, respectively.

The overall response rate (ORR) using the IWG 2006 criteria, in 29 HMA naïve patients, was 90%; including 10 patients (34%) with Complete Remission (CR). Among the 26 evaluable HMA-

failed patients the ORR was 54% including 8% CR or PR. The median time to initial and best response were 1 and 4 cycles in the HMA naïve group and 2 and 5 cycles in the HMA failed group.

The safety population (n = 74) received at least 1 dose of oral rigosertib. The combination was well tolerated. Other than genitourinary adverse events (AEs), the AE profile was similar to those described for azacitidine alone in this patient population. Genitourinary AEs, including hematuria (45% incidence of all grades, including 9% grade 3, and dysuria (38% all grades and 9% grade 3) were observed. A Safety Optimization Strategy was implemented for the higher dose cohort of 1,120 mg of oral rigosertib. These strategies included earlier in the day administration of the PM dose, oral hydration, monitoring of urinary pH and mandatory bladder emptying at night. Collectively these strategies resulted in mitigation of the target genitourinary AEs, including reduction of genitourinary grade 3 AEs reported from an earlier cohort despite receiving a higher dose of oral rigosertib.

In conclusion, oral rigosertib in combination with azacitidine was well tolerated in HMA naïve and HMA failed HR-MDS patients. The combination produced an encouraging rate of overall response and complete remission in both groups. The safety optimization strategies and increased dose exploration of oral rigosertib in the combination is leading to the development of a pivotal Phase 3 trial in HMA and chemotherapy naïve patients.

Drs. Lewis Silverman and Guillermo Garcia Manero, the lead investigators of the study at Mount Sinai Medical Center and MD Anderson Cancer Center, respectively, commented, "This multi-institutional collaborative study based on earlier laboratory research showing synergistic activity of rigosertib in combination with azacitidine led to a clinical trial of this combination in higher-risk MDS patients for both HMA naive and failed patients. The high overall response rate reported today is impressive, as is the durability and rate of achieving complete remission. We are excited about progressing these studies to a randomized pivotal placebo-controlled Phase 3 trial. The overall tolerability of the combination and convenience of administration of oral rigosertib could be key advantages for these future studies."

Dr. Steve Fruchtman, President of Onconova Therapeutics, Inc, sponsor of this study and developer of rigosertib commented, "We are most grateful to the patients, their families and our dedicated collaborating investigators for their participation in this study. The impressive results presented here have led to our plan for a pivotal trial for these patients ultimately hoping to improve upon their current therapeutic options. Based on End of Phase 2 Meetings with the Health Authorities, we have developed a randomized controlled pivotal trial. We expect to start the regulatory process for the approval of this trial plan very shortly. We are hopeful that both intravenous and oral formulations of rigosertib will be useful in serving the needs of higher risk MDS patients".

This oral presentation was delivered by Shyamala Navada, MD, Mount Sinai Medical Center on Saturday, December 1, 2018.

A copy of the presentation is available by visiting the Scientific Presentations section of Onconova’s website.

Onconova plans to meet with the FDA to discuss the results of the Phase 2 trial and the planned Phase 3 trial, and to seek a Special Protocol Assessment. The Company has partnered rigosertib with SymBio Pharmaceuticals, for Japan and Korea, and with Pint Pharma for Latin American countries. Both partners have indicated their interest in participating in the proposed new pivotal Phase 3 trial by enrolling patients in their respective territories. SymBio is currently conducting Phase 1 studies with oral rigosertib in Japan and also participating in the Phase 3 global INSPIRE trial. The Company is also actively seeking additional collaborations for rigosertib in other geographies.