On September 20, 2018 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that Alan H. Auerbach, Chairman, Chief Executive Officer, President and Founder of Puma, will provide an overview of the Company at 1:10 p.m. EDT on Monday, October 1, at the Cantor Global Healthcare Conference (Press release, Puma Biotechnology, SEP 20, 2018, View Source [SID1234529505]). The conference will be held at the InterContinental New York Barclay Hotel.

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A live webcast of the presentation will be available on the Company’s website at www.pumabiotechnology.com. The presentation will be archived on the website and available for 30 days.

On September 20, 2018 Sesen Bio, Inc. (Nasdaq: SESN), a late-stage clinical company developing fusion protein therapies for the treatment of cancer, reported that the company will present its three-month Phase 3 VISTA Trial data during a poster session at the Global Congress on Bladder Cancer 2018 (Press release, Sesen Bio, SEP 20, 2018, View Source [SID1234529506]). The congress is being held Sept. 20-21, 2018 in Madrid. The ongoing VISTA registration trial is evaluating Vicinium, Sesen Bio’s lead product candidate, for the treatment of people with high-grade non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG).

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The data, which were presented during a plenary session at the American Urological Association Annual Meeting in May 2018, include a biomarker update showing that nearly all screened patient samples expressed EpCAM, the molecular target of Vicinium.

"We are delighted to present the three-month VISTA Trial data at the Global Congress on Bladder Cancer and further showcase the promise of Vicinium in treating people with NMIBC," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Today, patients who are unresponsive or become refractory to BCG therapy have virtually one option: complete removal of their bladder. This is a long, challenging and life-altering procedure with a high rate of mortality that nearly half of people who face it choose not to undergo. It is critically important that such people are provided an effective and tolerable option that spares them from having to make such a difficult decision and saves their bladder. We believe that Vicinium holds significant potential as a targeted treatment that could renew the lives of these underserved patients."

As announced in May, the three-month data are from 111 patients in the VISTA Trial 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. In an analysis assessing pooled CIS patients (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)1, Vicinium treatment resulted in a complete response rate of 42 percent at three months. In patients with papillary disease without CIS, treatment with Vicinium demonstrated a 68 percent recurrence-free rate at three months.

In addition, Vicinium has been well-tolerated in the VISTA Trial. Of the treatment-related adverse events in the three-month analysis, 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.

About Vicinium
Vicinium (also known as VB4-845), Sesen Bio’s lead product candidate, is a fusion protein being developed 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 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.

On September 20, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported its clinical data on tislelizumab, an investigational anti-PD-1 antibody, in Chinese patients with lung cancers, in two oral presentations at the 21st Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) in Xiamen, China (Press release, BeiGene, SEP 20, 2018, View Source;p=RssLanding&cat=news&id=2368376 [SID1234529526]).

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"Advanced lung cancer is one of our focus areas for development of tislelizumab, where we hope to have an impact on the way patients are treated both in China and worldwide. This complex and difficult-to-treat disease has proven to be susceptible to treatment with immunotherapies," commented Amy Peterson, M.D., Chief Medical Officer, Immuno-Oncology, at BeiGene. "The preliminary data presented today demonstrate that tislelizumab is generally well tolerated and has antitumor activity both as monotherapy and in combination with several chemotherapy regimens used in small cell and non-small cell lung cancer patients. We are hopeful that further study of tislelizumab may lead to a new treatment option for a broad array of patients with lung cancers."

Summary of Preliminary Results of Phase 2 Trial in China of Tislelizumab Combined with Chemotherapy as First-Line Treatment in Advanced Lung Cancer Setting

The multi-center, open-label Phase 2 trial in China (CTR20170361) of tislelizumab in combination with chemotherapy enrolled 54 patients with previously untreated locally advanced or metastatic lung cancer. All patients received tislelizumab at 200 mg every three weeks, plus platinum doublet until disease progression. Patients with non-squamous non-small cell lung cancer (NSCLC) (n=16) received pemetrexed plus platinum; patients with squamous NSCLC received either paclitaxel plus platinum (cohort A, n=15) or gemcitabine plus platinum (cohort B, n=6); and patients with small cell lung cancer (SCLC) received etoposide plus platinum (n=17).

As of the June 5, 2018 data cutoff, 35 patients remain on treatment. Treatment discontinuation due to adverse events (AEs) occurred in three patients. Fifty-one patients had at least one post-baseline tumor assessment and were evaluable for efficacy. Objective responses (including confirmed and unconfirmed partial responses) were observed in 56 percent (31 percent confirmed; all patients with an unconfirmed partial response remained on treatment) of 16 evaluable patients with non-squamous NSCLC; 80 percent (all confirmed) in 15 evaluable patients with squamous NSCLC, cohort A; 67 percent (all confirmed) in six patients with squamous NSCLC, cohort B; and 82 percent (47 percent confirmed; all patients with an unconfirmed partial response remained on treatment) in 17 evaluable patients with SCLC. Data continue to mature with follow-up.

AEs were considered manageable and reversible, with chemotherapy dose modifications or tislelizumab dose holds, except for one fatal event of myocarditis/myositis. Five patients (9.3%) experienced at least one grade ≥3 AE (polymyositis, dyspnea, rhabdomyolysis, myocarditis/myositis, and myasthenia gravis) that were considered to be possibly related to tislelizumab. Immune-related AEs (irAEs) occurred in 13 patients (24%) and included hypothyroidism (n=3), decreased tri-iodothyronine (n=2), hyperthyroidism (n=2), pneumonitis (n=2), pyrexia (n=2), and rash (n=2).

"We are excited by the preliminary data of tislelizumab combined with chemotherapy in patients with advanced lung cancer. The safety and tolerability appear consistent with previous data, and high response rates of up to 80 percent in a squamous NSCLC cohort along with low discontinuation rates support continued investigation of tislelizumab in patients with advance lung cancer. We are hopeful that this combination therapy will offer improved outcomes in this advanced disease setting," said Professor Jie Wang, M.D., from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China, and lead author of the presentation.

Summary of Preliminary Results of Tislelizumab in Chinese Patients with NSCLC from Phase 1/2 Trial

The multi-center, open-label Phase 1/2 trial in China (CTR20160872) of tislelizumab enrolled 46 patients with NSCLC in the Phase 2 indication expansion portion of the trial, with 21 patients having expression of PD-L1 in 10 percent or more of their tumor cells (PD-L1+); the remaining 25 patients were considered PD-L1 negative (PD-L1-).

As of the May 11, 2018 data cutoff, 15 patients (33%) remained on treatment with the median treatment duration of 4.1 months (0.2–11.3 months) and a median follow-up of 8.4 months (0.2–11.8 months). Treatment discontinuation due to adverse events (AEs) occurred only in one patient. The median duration of treatment was 3.5 months (0.2-11.2 months) and 4.4 months (0.7–11.3 months) in PD-L1+ and PD-L1- cohorts, respectively. A total of 42 patients had at least 1 post-baseline tumor assessment and were evaluable for antitumor activity. Confirmed partial responses were observed in 17 percent of the evaluable patients, including 12 percent and 20 percent in PD-L1+ and PD-L1- patients, respectively.

Across the two arms, the most common treatment-related AEs (TRAEs) (occurring in ≥ 10% of patients) were increased transaminases (26%), rash (11%) and hypothyroidism (11%). A total of 14 patients had serious AEs and three of these patients experienced serious TRAEs, including nausea and vomiting (n=1), increased aspartate aminotransferase (AST) (n=1) and hyperglycemia (n=1). Three patients experienced a serious AE with a fatal outcome (multiple organ dysfunction syndrome [n=1], central nervous system metastases [n=1], hypotension [n=1]); none were determined to be related to treatment. Immune-related AEs occurred in 26 patients (57%) and many were overlapping with the TRAE cases.

"The prognosis for patients with late stage non-small cell lung cancer remains particularly poor. We are pleased that this trial demonstrated that treatment with tislelizumab was generally well tolerated. We are excited to see that Phase 3 trials evaluating tislelizumab, either as monotherapy or in combination with chemotherapy, in patients with advanced NSCLC are underway and look forward to the results," said Yi-Long Wu, M.D., President of Chinese Thoracic Oncology Group (CTONG) and lead author of the presentation.

Trial data with the same cut off time will be presented at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC), which takes place September 23-26 in Toronto.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. Discovered by BeiGene scientists in Beijing, tislelizumab is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has demonstrated high affinity and specificity for PD-1. It is potentially differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells, based on preclinical data. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumor cancers outside of Asia (except Japan).

On September 20, 2018 Exicure, Inc. (OTCQB:XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing three-dimensional spherical nucleic acid (SNA) constructs, reported Phase 1 results for AST-008, an SNA consisting of toll-like receptor 9 (TLR9) agonists designed for immuno-oncology applications (Press release, Exicure, SEP 20, 2018, View Source;p=RssLanding&cat=news&id=2368198 [SID1234529613]).

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"Phase 1 results for AST-008 demonstrated our desired highly potent immune system activation without serious adverse events or dose limiting toxicity. We believe this molecule could lead to better combination therapies for patients with cancer and, to that end, we expect to initiate a Phase 1b/2 trial in patients before year end," said Dr. David Giljohann, Chief Executive Officer of Exicure. "These data support the potential of our SNA platform for immuno-oncology and set the stage for ongoing development of the SNA platform into indications well beyond cancer."

Exicure’s Phase 1 Trial Results

The Phase 1 trial of AST-008 was a single ascending subcutaneous dose trial comprised of 16 healthy volunteers. AST-008 was shown to be safe and tolerable in all subjects, with no serious adverse events and no dose limiting toxicity. AST-008 was well tolerated and all AST-008-related adverse events were of short duration, reversible and consistent with TLR9 activation.

In addition to the principle safety and tolerability endpoint, the trial screened for levels of select cytokines and markers of immune cell activation. AST-008 was shown to elicit high levels of certain cytokines as well as activate important effector cells of the immune system including T cells and natural killer cells, the main drivers of anti-tumor response.

For the four subjects receiving the trial’s top dose of about 20 µg/kg of AST-008, initial analyses suggest that the average fold-increase above baseline for these cytokines is approximately as follows: IFN-gamma: 3 fold; IL-6: 57 fold; IL-12: 2 fold; IP-10: 32 fold; and MCP-1: 4 fold. At this dose, AST-008 also elicited 9.5 fold and 3.5 fold increases in the fraction of activated T cells and natural killer cells, respectively, compared to baseline.

Exicure’s Planned Phase 1b/2 Patient Trial

Exicure intends to begin an open-label Phase 1b/2 trial of intra-tumorally dosed AST-008 in combination with a checkpoint inhibitor before year end. The trial will begin with an AST-008 dose finding Phase 1b stage, followed by a Phase 2 expansion stage. In the Phase 1b, Exicure will enroll patients with superficial injectable tumors and will prioritize those with Merkel cell carcinoma, cutaneous squamous cell carcinoma, melanoma, and squamous cell carcinoma of the head and neck. Preliminary data from the Phase 1b stage are expected in late 2019.

Historical TLR9 Agonist Healthy Volunteer Data

In 2015, Mologen AG published results (European Journal of Cancer, 2015, volume 51, supplement 1, page S12) from a healthy volunteer trial. In a single cohort, 13 subjects each received one 60 mg dose (equivalent to 923 µg/kg for a 65 kg subject) of lefitolimod subcutaneously. On average, across the cohort, there was a 7 fold-increase in IP-10 expression above baseline. No cell activation data were reported. Lefitolimod is currently in a Phase 3 clinical trial.

In 2004, Coley Pharmaceutical Group (now Pfizer, Inc.) published results (Journal of Immunotherapy, 2004, Volume 27, pages 460–471) from a single ascending dose healthy volunteer trial. In that trial, their TLR9 agonist, PF-03512676, was administered subcutaneously to six subjects per dose level. For the 20 µg/kg dose level, the average fold-increase above baseline for these cytokines is as follows: IFN-gamma: no change from baseline; IL-6: 8 fold; IL-12: no change from baseline; IP-10: 9 fold; and MCP-1: 3 fold.

Upcoming Presentations

Exicure management expects to be presenting and available for meetings at a number of fall investor conferences including:

October 2 – Ladenburg Thalmann 2018 Healthcare Conference at the Sofitel Hotel New York, NY;
October 3 – Leerink Partners Roundtable Series: Rare Disease & Oncology at the Lotte New York Palace, New York, NY;
October 9 – Chardan’s 2nd Annual Genetic Medicines Conference at the Westin Grand Central, New York, NY;
October 25 – BTIG Biotech Conference at the Langham Hotel, New York, NY.

On September 20, 2018 AIVITA Biomedical reported that it has dosed its first of 10 patients currently enrolled as part of its Phase 2 trial in patients with advanced ovarian cancer (Press release, AIVITA Biomedical, SEP 20, 2018, View Source [SID1234529879]). The trial is designed to investigate AIVITA Biomedical’s patient-specific cancer treatment consisting of autologous dendritic cells loaded with autologous antigens from the patient’s tumor-initiating cells.

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AIVITA is enrolling approximately 99 patients in the Company’s ROOT OF CANCER ovarian cancer trial to be randomized in a 2:1 ratio to receive either the Company’s patient-specific cancer treatment or a control agent consisting of autologous monocytes. The treatment will be administered in a series of injections along with standard care.

"We’re proud of the manufacturing team here at AIVITA who have made this important moment possible," said Dr. Bob Dillman, Chief Medical Officer at AIVITA. "The team has contributed manufacturing efficiencies which have greatly improved the success rate and speed of creating this treatment, allowing us to treat more patients more reliably. We’ve since randomized several additional patients in this trial and activity is accelerating as we sign on more hospitals and receive additional tumors."

Previously, this treatment was tested in two Phase 2 trials in patients with advanced melanoma and approved for Phase 3 testing. The first Phase 2 trial demonstrated a 54% 5-year survival rate compared to a 29% 5-year survival rate for an active control arm. The second randomized Phase 2 trial demonstrated similar results, with a significantly longer median survival compared to the control arm.

AIVITA’s ROOT OF CANCER technology is also the subject of an ongoing Phase 2 clinical trial treating glioblastoma in the USA. The Company is also currently applying for conditional approval to commercialize the treatment for melanoma in Japan and is considering Japanese strategic partners for this program.

About Ovarian Cancer

Ovarian cancer is the fifth most common cause of female cancer deaths, with an estimated 22,240 new diagnoses in 2018 and 14,070 deaths. The median age at diagnosis is 63, with a 5-year survival rate of less than 50% for all, and about 35% for the two thirds who have advanced disease (stage III or IV) at the time of initial diagnosis. Current standard of care includes surgical debulking and several courses of chemotherapy.

About ROOT OF CANCER

AIVITA’s treatment is a platform technology applicable to most solid tumor types and consists of autologous dendritic cells loaded with autologous tumor antigens from autologous self-renewing tumor-initiating cells.

The ovarian Phase 2 double-blind study will enroll approximately 99 patients who will be randomized in a 2:1 ratio to receive either the autologous dendritic cell vaccine or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy.

For additional information about AIVITA’s AVOVA-1 trial patients can visit www.clinicaltrials.gov/ct2/show/NCT02033616