PharmaCyte Closing in on Submission of Crucial Investigational New Drug Application to Begin Clinical Trial in Pancreatic Cancer

On May 21, 2018 PharmaCyte Biotech (OTCQB: PMCB) reported it has reached the proverbial "home stretch" regarding its efforts to submit an Investigational New Drug Application (IND) to the U.S. FDA (Press release, PharmaCyte Biotech, MAY 21, 2018, View Source [SID1234526825]). It’s an IND that has been eagerly anticipated by the company’s shareholders since PharmaCyte met with the FDA in early 2017, and it would lay out PharmaCyte’s planned Phase 2b clinical trial for the treatment of locally advanced, non-metastatic, inoperable pancreatic cancer or LAPC.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The key to submitting the IND is and always has been satisfying regulatory requirements. In short, PharmaCyte must generate the necessary data that the FDA requires for any treatment—but especially a treatment that is deemed a "biologic" by the FDA and comprised of living cells that would be placed inside a human’s body.

PharmaCyte just announced that it has completed and passed 29 different tests from its Master Cell Bank (MCB), which is made up of cells that will be used in its planned clinical trial in patients with LAPC. The successful completion of these tests is the final hurdle before encapsulation and testing of the encapsulated cells can begin at Austrianova.

Vials of cells from the MCB have already been supplied to the company’s partner, Austrianova, for encapsulation. Austrianova will now be charged with completing the encapsulation process using PharmaCyte’s signature live-cell encapsulation technology, Cell-in-a-Box, to create the thousands of capsules that will be necessary to conduct its planned clinical trial. Each capsule will contain 10,000 live cells, and then each syringe will be filled with 300 capsules—making up the finished product that will be sent to clinical trial sites.

The encapsulation process will be followed by a battery of tests that will generate the necessary data to satisfy regulatory requirements and should complete what has been a long, meticulous process and allow PharmaCyte to finally submit it’s IND to the FDA.

In addition to the 29 successful tests that PharmaCyte announced last week, the company has stated that a number of additional tests have also been a success (See www.PharmaCyte.com/news). This is all very good news for shareholders who have been clamoring for the start of a clinical trial, and it should bode well for a company that is trying to win the FDA’s approval when it does submit its IND.

PharmaCyte’s goal of starting a Phase 2b clinical trial to meet an unmet medical need in the treatment of patients with LAPC is a remarkable milestone for such a small company, and because their first ever trip inside the clinic involves presenting the FDA with a biologic treatment, the sheer complexity of this journey explains why the process has been so time consuming. PharmaCyte’s treatment for LAPC utilizes genetically engineered live human cells that produce a particularly potent cytochrome P450 enzyme that is able to activate the chemotherapy prodrug ifosfamide.

As previously mentioned, these cells are encapsulated using the Cell-in-a-Box technology, and the tiny, pinhead-sized capsules are implanted near the cancerous tumor so that a high local concentration of the cancer-killing ifosfamide metabolite is produced near the tumor.

PharmaCyte’s treatment is not a single molecule drug. It’s not a drug at all actually. And because the treatment is made up of live human cells that are responsible for activating an already FDA-approved chemotherapy drug, the FDA expects every single cell to act exactly the same way, every single time, in every single test that PharmaCyte is required to conduct.

The FDA simply wants to know that the capsules and the cells that live inside them will remain exactly the same at all times when they are eventually placed inside the human body. And unfortunately there is no short cut when it comes to satisfying regulatory requirements.

The unmet medical need that PharmaCyte expects to address in its clinical trial is for those patients who no longer see any benefit from using the preferred standard of care, Abraxane combined with gemcitabine, or FOLFIRINOX, another combination chemotherapy that is increasingly being used in the U.S. as the preferred standard of care. These patients must have tumors that no longer respond to these combination chemotherapies after they’ve been on the treatment for a period of between 4 and 6 months.

The good news for PharmaCyte’s patient shareholders is that the company has reached the "end of the line" in what has been a very long process. But, when it comes to the FDA and success in a clinical trial—especially for a small company like PharmaCyte—there is only one true shot at getting it right.

Stock Market Media Group will be interviewing PharmaCyte’s CEO, Kenneth L. Waggoner, and its Chief Scientific Officer, Prof. Dr. Walter H. Günzburg, to discuss the IND, encapsulation, testing, preparations for the upcoming planned clinical trial, among other topics. The radio-style interview will be released and announced publicly via a press release within the next 2 weeks.

Inovio Opens Phase 2 Trial for VGX-3100 in Third Indication To Treat HPV – The No. 1 Sexually Transmitted Disease

On May 21, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that it has commenced a Phase 2 clinical trial to evaluate the efficacy of VGX-3100 in adult men and women with human papilloma virus (HPV)-related anal dysplasia (Press release, Inovio, MAY 21, 2018, View Source;The-No-1-Sexually-Transmitted-Disease/default.aspx [SID1234526823]). Recruitment is ongoing for patients who are HIV-negative with histologically confirmed anal or perianal high-grade squamous intraepithelial lesions (HSIL) associated with HPV-16 and/or HPV-18. The study is planning to enroll approximately 24 patients and will administer at least three doses of VGX-3100.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Anal HSIL or dysplasia is the precursor to anal cancer, which is estimated to cause more than 1,100 deaths in the United States in 2018. Currently, the only treatments for anal dysplasia consist of surgical excision, electro-cautery or laser therapy, but more than 50% of those treated with these current treatments experience recurrence of the disease.

Dr. Céline Bouchard, FRCSC, gynecologist, colposcopist and Coordinating Principal Investigator, said, "The large burden of disease rests in the general population. As more than 70% of anal cancers in the United States occur among HIV-negative men and women, a non-surgical immunotherapy to eradicate precancerous perianal and/or anal lesions caused by HPV types 16 or 18 infection would represent a major breakthrough for the treatment of this disease and the prevention of anal cancer."

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "Inovio is boldly targeting the world’s No. 1 sexually transmitted disease – the HPV virus – across the continuum of conditions with our treatment that has demonstrated efficacy eliminating disease and clearing the underlying HPV infection. This compact Phase 2 efficacy trial represents an important step towards Inovio’s aim to develop a comprehensive immunotherapeutic solution to HPV-related diseases, especially given that anal dysplasia remains an underdiagnosed condition which needs better treatment options. Inovio is rapidly moving on a path to become the ‘go-to’ immunotherapeutic solution provider for all diseases caused by HPV, including cervical, vulvar and anal precancers and with our partner MedImmune/AstraZeneca for HPV-related cancers."

This open-label, multi-center Phase 2 study is designed to evaluate the safety and efficacy of VGX-3100 administered by intramuscular (IM) injection w CELLECTRA delivery system in adult men and women who are human immunodeficiency virus (HIV) negative with HSIL associated with HPV-16 and/or HPV-18. Prior study results utilizing Inovio’s VGX-3100 immunotherapy, which is also in a Phase 3 trial evaluating treatment for cervical dysplasia, supported expanding treatment indications for patients associated with HPV-16 and/or HPV-18. In a Phase 2 trial for cervical dysplasia, VGX-3100 demonstrated a systemic response (vs. localized surgery) and clearance of cervical lesions and eliminating the underlying HPV infection in many patients. For additional information about the study, please visit www.clinicaltrials.gov (search identifier NCT03499795).

About VGX-3100

VGX-3100 is a DNA-based immunotherapy under Phase 3 investigation for the treatment of HPV-16 and HPV-18 infection and precancerous lesions of the cervix. Inovio is in open-label Phase 2 clinical trials evaluating its efficacy for treating HPV-related vulvar and anal precancers. VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for precancerous 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 precancerous 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 precancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

About Inovio’s DNA Immunotherapy Technology Platform

Inovio is advancing the medical potential of a unique class of immunotherapy technology. Its DNA-based platform, which is the foundation for all of Inovio’s products, including VGX-3100, is unique in its ability to leverage the body’s naturally existing mechanisms to generate robust, highly targeted immune responses to prevent and treat disease – and to do so in the body without harmful side effects. Its SynCon immunotherapy design and CELLECTRA delivery transform novel genetic blueprints into functional antibody and killer T cell responses. Inovio was the first to report the activation – in the body – of significant, antigen-specific functional T cells correlated to statistically significant efficacy in a placebo-controlled, randomized, double-blind Phase 2b clinical trial (HPV-related precancer), with a very favorable safety profile. These data were published in The Lancet and independently described as a "major breakthrough" in the field by U.S. National Cancer Institute scientists. Inovio has achieved significant antigen-specific immune responses against multiple diseases and is advancing a growing pipeline of cancer and infectious disease immunotherapies and vaccines.

Evotec and Celgene enter into strategic oncology partnership

On May 21, 2018 Evotec AG (Frankfurt Stock Exchange, Prime Standard, ISIN: DE 000 566480 9, WKN 566480) reported that Evotec and Celgene Corporation ("Celgene") have entered into a long-term strategic drug discovery and development partnership to identify new therapeutics in oncology (Press release, Evotec, MAY 21, 2018, View Source;announcements/ad-hoc-releases/p/evotec-and-celgene-enter-into-strategic-oncology-partnership-5685 [SID1234526821]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the agreement, Evotec will receive an upfront payment of $ 65 m and may be eligible to receive significant milestone payments as well as tiered royalties on each licensed programme. Celgene receives exclusive opt-in rights to license worldwide rights to all programmes developed within this collaboration.

Contact: Dr Werner Lanthaler, Chief Executive Officer, Evotec AG, Manfred Eigen Campus, Essener Bogen 7, 22419 Hamburg, Germany, Phone: +49.(0)40.560 81-242, [email protected]

Phase 3 Registration Trial for Non-Muscle Invasive Bladder Cancer Achieves 42% Complete Response Rate at Three Months in Carcinoma in Situ Patients

On May 21, 2018 Sesen Bio, Inc. (NASDAQ: SESN), a late-stage clinical company advancing next-generation antibody-drug conjugate (ADC) therapies for the treatment of cancer, reported positive, three-month data from its ongoing Phase 3 VISTA Trial of Vicinium for the treatment of patients with high-grade non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG) (Press release, Eleven Biotherapeutics, MAY 21, 2018, View Source [SID1234526819]). The efficacy data being reported are based on three-month follow-ups from 111 patients with high-grade NMIBC that is either carcinoma in situ (CIS), which is cancer found on the inner lining of the bladder that has not spread into muscle or other tissue, with or without papillary disease, or from patients with papillary disease without CIS, which is cancer that has grown from the bladder lining out into the bladder, but has not spread into muscle or other tissue.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"High-grade NMIBC is a devastating cancer that typically occurs later in life and for which treatment options are limited. Over the last 30 years, our industry has seen little innovation for the treatment of this prevalent cancer. The current standard-of-care, BCG, works in many patients, but many will also eventually relapse. For those patients who relapse or who don’t respond at all, the standard alternative is radical cystectomy. In a cystectomy, the bladder is removed along with surrounding lymph nodes and other organs that contain cancer. I am very encouraged by both the safety and these three-month efficacy data with Vicinium, and I look forward to continuing to work with the Sesen Bio team to help bring forward this potential treatment as a safe and effective option for my patients," said Rian Dickstein, M.D. F.A.C.S., chief of urology, University of Maryland Baltimore Washington Medical Center; medical director of GU oncology, Tate Cancer Center at The University of Maryland Baltimore Washington Medical Center​; clinical assistant professor, Department of Surgery, University of Maryland School of Medicine; director, bladder cancer program, Chesapeake Urology; and an investigator in the VISTA Trial.

"The VISTA Trial three-month data are encouraging for our company and the patients with high-grade NMIBC who have been underserved for many years," said Stephen Hurly, president and chief executive officer of Sesen Bio. "We have made tremendous progress over the last several years to get us to where we are today, and I am proud of what our team has accomplished. Our new name is a reflection of the journey we’ve taken to get to this point and represents our

1

sesnauadataprvfinalimage1.jpg

mission of improving lives. With 12-month data expected by mid-2019, we are continuing to advance Vicinium to assess its full potential in treating this devastating cancer."

VISTA Trial Design and Patient Cohorts
The Phase 3 VISTA Trial completed recruitment in March 2018 with a total of 133 patients with high-grade NMIBC that is either CIS or papillary with or without CIS, who have been previously treated with BCG. The primary endpoint of the trial is the complete response rate in patients with CIS with or without papillary disease.

The clinical trial includes three patient cohorts based on histology and time to recurrence after adequate BCG:

Cohort 1 (n=87): patients with CIS with or without papillary disease whose cancer recurred within six months of their last course of BCG treatment.

Cohort 2 (n=6): patients with CIS with or without papillary disease whose cancer recurred after six months, but before 11 months, after their last course of BCG treatment.

Cohort 3 (n=40): patients with papillary disease without CIS whose cancer recurred within six months of their last course of BCG treatment.
Three-Month Efficacy Results: CIS Patients
In cohort 1, 72 patients were evaluable for three-month data as of the April 20, 2018 data cut-off date. In these patients, treatment with Vicinium demonstrated a complete response rate of 39 percent. In evaluable patients in cohort 2 (n=5), treatment with Vicinium demonstrated a complete response rate of 80 percent. In an analysis assessing pooled CIS patients from cohorts 1 and 2 (n=77), based on final U.S. Food and Drug Administration guidance on treatment of BCG-unresponsive CIS NMIBC patients (defined as patients with recurrent CIS within 12 months of adequate BCG therapy), Vicinium treatment resulted in a complete response rate of 42 percent at three months.

Three-Month Efficacy Results: Papillary Patients
Patients with papillary disease without CIS were enrolled in cohort 3, but are not included in the primary endpoint assessment. At screening, all of these patients underwent mandatory resection of their tumors and upon starting treatment, were deemed to have no visible evidence of disease. As such, in this patient population, rates of disease recurrence and time to disease recurrence are standard criteria to evaluate response. In these evaluable patients (n=34), treatment with Vicinium demonstrated a 68 percent recurrence-free rate at three months.

Preliminary Safety Results
To date, Vicinium has been well-tolerated in the VISTA Trial. In treated patients across cohorts (n=129), 72 percent of all adverse events were Grade 1 or 2. The most commonly reported treatment-emergent adverse events (all grades) were urinary tract infection (29%), dysuria (19%), hematuria (16%), pollakiuria (12%), diarrhea (10%), fatigue (10%), micronutrition urgency (9%), nausea (8%) and increased lipase (8%, all asymptomatic). Of the treatment-related adverse events, four percent were Grade 3 or 4, with no Grade 5 treatment-related adverse events. Four treatment-related serious adverse events were reported, including acute kidney injury or renal failure and cholestatic hepatitis.

"The positive, three-month data from the VISTA Trial support Vicinium’s potential to offer a new and completely different treatment option for patients who need it," said Donald L. Lamm, M.D., BCG Oncology, P.C., Phoenix. "In contrast to the many other advances in cancer therapy, treatment for high-grade NMIBC has suffered from little innovation, and Vicinium represents a unique approach with a targeted protein, an entirely new mechanism for treating this disease. I believe this new treatment approach, which has demonstrated a 42 percent, three-month complete response rate in patients who have failed to respond to BCG and good tolerability, gives these patients new hope for beating bladder cancer without life-changing major surgery. High-grade NMIBC patients have a high chance of losing their bladder after having gone through unreliable and often difficult treatments. I believe that Vicinium, a first-in-class, innovative therapy, may change that in the future."

Conference Call Information
To participate in the conference call, please dial (844) 831-3025 (domestic) or
(315) 625-6887 (international) and refer to conference ID 4453267. The webcast can be accessed in the Investor Relations section of the company’s website at www.sesenbio.com. The replay of the webcast will be available in the investor section of the company’s website at www.sesenbio.com for 60 days following the call.

About the VISTA Clinical Trial
The VISTA Trial is an open-label, multicenter, single-arm Phase 3 clinical trial evaluating the efficacy and tolerability of Vicinium in patients with high-grade non-muscle invasive bladder cancer (NMIBC) that is carcinoma in situ (CIS), which is cancer found on the inner lining of the bladder that has not spread into muscle or other tissue) and/or papillary, which is cancer that has grown from the bladder lining out into the bladder but has not spread into muscle or other tissue, who have been previously treated with bacillus Calmette-Guérin (BCG). The primary endpoint of the trial is the complete response rate in patients with CIS with or without papillary disease. Patients in the trial receive locally administered Vicinium twice a week for six weeks, followed by once-weekly treatment for another six weeks, then treatment every other week for up to two years. Twelve-month data are anticipated in mid-2019. To learn more about the Phase 3 VISTA Trial, please visit www.clinicaltrials.gov and search the identifier NCT02449239.

About Vicinium
Vicinium, also known as VB4-845, is Sesen Bio’s lead product candidate and is a next-generation antibody-drug conjugate (ADC), developed using the company’s proprietary Targeted Protein Therapeutics platform, for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA). Vicinium is constructed with a stable, genetically engineered peptide linker to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression

observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA Trial, designed to support the registration of Vicinium for the treatment of high-grade NMIBC in patients who have previously received two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Twelve-month data from the trial are anticipated in mid-2019. Additionally, Sesen Bio believes that Vicinium’s cancer cell-killing properties promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicinium in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

About Non-Muscle Invasive Bladder Cancer
Bladder cancer is the sixth most commonly diagnosed cancer in the United States, and approximately 80 percent of patients have non-muscle invasive bladder cancer (NMIBC). In NMIBC, cancer cells are in the lining of the bladder or have grown into the lumen of the bladder but have not spread into muscle or other tissue. NMIBC primarily affects men and is associated with carcinogen exposure. Initial treatment includes surgical resection; however, there is a high rate of recurrence and more than 60 percent of all patients diagnosed with NMIBC will receive bacillus Calmette-Guérin (BCG) immunotherapy. While BCG is effective in many patients, challenges with tolerability have been observed and many patients will experience recurrence of disease. If BCG is not effective or a patient can longer receive BCG, the recommended option for treatment is radical cystectomy, the complete removal of the bladder.

Athenex to Present at UBS Global Healthcare Conference

On May 21, 2018 Athenex, Inc. (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that management will present at the UBS Global Healthcare Conference in New York, NY, on Monday, May 21st, at 3:00 pm EST (Press release, Athenex, MAY 21, 2018, View Source;p=RssLanding&cat=news&id=2349986 [SID1234526816]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation will be webcasted, and can be accessed at the Investor Relations section of the Company’s website, located at www.athenex.com. An archive will be available at this website until August 19, 2018.