On December 15, 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 that updated clinical data from an ongoing Phase 1A/1B trial of tislelizumab, an investigational anti-PD-1 antibody, were presented in an oral session and a poster at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress, being held December 13-16 in Geneva, Switzerland (Press release, BeiGene, DEC 15, 2018, View Source;p=RssLanding&cat=news&id=2380786 [SID1234532073]).

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"We continue to be pleased with the results of tislelizumab in solid tumors," commented Amy Peterson, M.D., Chief Medical Officer, Immuno-Oncology, at BeiGene. "We believe that these updated results provide support for the continued development of tislelizumab in patients with bladder, esophageal, stomach, liver and non-small cell lung cancers, and we have registration-enabling studies ongoing or planned to start soon in each of these indications."

Summary of ESMO (Free ESMO Whitepaper)-IO Presentations from the Ongoing Phase 1A/1B Trial
The multi-center, open-label Phase 1A/1B trial (NCT02407990) of tislelizumab as monotherapy in advanced solid tumors is being conducted in Australia, New Zealand, the United States, Taiwan and South Korea and consists of dose-escalation and dose-expansion phases in disease-specific cohorts.

Updated Results in Patients with Urothelial Carcinoma (UC)
Data presented at ESMO (Free ESMO Whitepaper)-IO included updated results from an analysis of tislelizumab in 17 patients with UC. At the time of the data cutoff on August 31, 2018, median treatment duration was 4.1 months (0.7-30.4 months), with two patients still on treatment.

Treatment-related adverse events (TRAEs) as assessed by the investigator occurred in 15 patients (88.2%). Of those, fatigue (n=5), infusion-related reactions (n=3), rash (n=3), nausea (n=2), pain in extremity (n=2), peripheral adema (n=2), and proteinuria (n=2) occurred in two or more patients. Three treatment-related Grade 3 or 4 AEs occurred in two patients, fatigue (n=1), and hyperglycemia and latent autoimmune diabetes (n=1). One patient discontinued treatment due to recurrent infusion-related reactions considered related to tislelizumab.

At the time of the data cutoff, all 17 patients were evaluable for response, defined as having a baseline tumor assessment with at least one post-baseline tumor response assessment, or progression or death. The confirmed response rate was 29.4 percent, with one complete response (CR) and four partial responses (PR). Three additional patients achieved stable disease (SD) as their best response. There was one CR, one PR and one SD among the eight patients with PD-L1 high tumors and two PRs and two SDs among the eight patients with PD-L1 low or negative tumors (one tumor was not-evaluable for PD-L1 expression). The median duration of response was 18.7 months (6.2-18.7 months).

Updated Results in Patients with Esophogeal, Gastric, Hepatocellular and Non-Small Cell Lung Cancers
In an oral presentation at ESMO (Free ESMO Whitepaper)-IO, data on patients with esophageal (EC, n=54), gastric (GC, n=54), hepatocellular (HC, n=50) and non-small cell lung cancers (NSCLC, n=49) were reported.

TRAEs occurring in at least five percent of patients across all cohorts included fatigue (8.7%), pruritis (7.7%), hypothyroidism (7.2%), decreased appetite (6.8%), rash (6.8%) and nausea (6.3%). Ten patients experienced one or more serious adverse events considered related to tislelizumab, including pneumonitis (n=3) and one case each of acute hepatitis, dermatitis, diarrhea, increased ALT, increased AST, infusion-related reaction, pyrexia and vomiting. Grade 3 or 4 TRAEs occurring in more than one patient included increased AST (n=4), increased ALT (n=3) and pneumonitis (n=2). There were two fatal TRAEs reported, including acute hepatitis in a patient with HCC confounded by rapidly progressive disease, and pneumonitis in a patient with NSCLC with compromised pulmonary capacity at baseline.

Confirmed response rates and disease control rates in patients with EC were 11.1 percent and 37.0 percent, respectively; 13.0 percent and 29.6 percent in patients with GC, respectively; 12.2 percent and 51.0 percent in patients with HCC, respectively, and 13.0 percent and 63.0 percent in patients with NSCLC, respectively. For patients with EC and NSCLC, the median duration of response (mDOR) had not been reached. The mDOR in patients with GC was 8.5 months and for patients with HCC it was 15.7 months.

About Tislelizumab
Tislelizumab (BGB-A317) is an investigational humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Discovered by BeiGene scientists, 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. The new drug application (NDA) for tislelizumab in China for patients with relapsed/refractory (R/R) classical Hodgkin’s lymphoma (cHL) has been accepted by the China National Medical Products Administration (NMPA, formerly known as CFDA) and granted priority review status. BeiGene and Celgene Corporation have a global strategic collaboration for the development of tislelizumab in solid tumors in the United States, Europe, Japan and the rest of world outside Asia.

On December 15, 2018 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported its results indicating that tab-cel (tabelecleucel) was generally well tolerated with responses for patients with Epstein-Barr virus-associated leiomyosarcoma (EBV+ LMS) (Press release, Atara Biotherapeutics, DEC 15, 2018, View Source [SID1234532076]). EBV+ LMS is a rare soft tissue sarcoma that occurs in transplant and immunosuppressed patients and is typically an aggressive radiation- and chemotherapy-resistant disease with poor patient outcomes. The results were presented in an oral session at the European Society for Medical Oncology Immuno-Oncology (ESMO I‑O) Congress 2018 taking place in Geneva, Switzerland.

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"The EBV+ LMS results presented at ESMO (Free ESMO Whitepaper) I-O are the second example, along with nasopharyngeal carcinoma (NPC), of a difficult-to-treat, EBV-associated solid tumor with encouraging responses to tab‑cel," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Observations of responses based on standard-CT and metabolic PET-CT imaging, in the context of prolonged survival, further highlight the opportunity for tab‑cel and off-the-shelf, allogeneic T-cell immunotherapy in EBV-associated cancers beyond our ongoing studies for patients with post‑transplant lymphoproliferative disease (PTLD) and NPC."

The oral presentation summarized the evaluation of tab-cel in an analysis of EBV+ LMS patients from three clinical studies, 2 single-center, open-label studies (NCT00002663, NCT01498484) and the multi‑center expanded access protocol (EAP) study (NCT02822495). Twelve patients with EBV+ LMS received one or more doses of tab-cel, of whom 10 were assessed for responses with two patients not evaluable. Two of the 10 patients achieved a partial response via CT-based RECIST 1.1 criteria and eight patients achieved stable disease. In the two single-center studies with longer follow-up, six of eight patients survived more than 27 months and the estimated median survival was 77.4 months. At the time of this analysis, responses assessed by PET-CT imaging were available from the multi-center EAP study where 3 of the 4 patients achieved a metabolic response. Tab-cel was generally well tolerated and the safety appeared consistent with a favorable risk profile and previous clinical studies.

About tab-cel (tabelecleucel)
Atara’s most advanced T-cell immunotherapy in development, tab-cel, is a potential treatment for patients with Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (EBV+ PTLD) who have failed rituximab, as well as other EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, the FDA granted tab-cel Breakthrough Therapy Designation for EBV+ PTLD following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tab-cel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. In addition, tab-cel has orphan status in the U.S. and EU. Tab-cel is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant (MATCH study) or solid organ transplant (ALLELE study), and Atara recently initiated a Phase 1/2 study in NPC.

On December 14, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported safety and promising activity of BPX-601 in Part 1 of a Phase 1/2 dose-escalation study in patients with advanced, metastatic pancreatic cancer expressing PSCA (prostate stem cell antigen) (Press release, Bellicum Pharmaceuticals, DEC 14, 2018, View Source [SID1234532061]). BPX-601 is a novel GoCAR-T cell candidate incorporating Bellicum’s co-activation domain, iMC, designed to boost T cell proliferation and persistence via administration of rimiducid. Data were reviewed during an oral presentation at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO) held in Geneva, Switzerland from December 13-16.

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"These initial results in advanced pancreatic cancer suggest that having greater control over the expansion and persistence of therapeutic cells may provide unique treatment benefits. We have observed promising initial clinical activity with BPX-601 in patients with one of the most challenging solid tumors, where there is a critical need for better treatments," commented Carlos R. Becerra, M.D., lead study investigator and oncologist and medical director of the Innovative Clinical Trials Center at Baylor University Medical Center at Dallas. "I am looking forward to the next phase of our study, which allows for a standard lymphodepletion regimen and administration of multiple doses of rimiducid to further increase the expansion and persistence of BPX-601 cells and the potential for greater impact against pancreatic and other tumor types."

Study Overview
A total of 12 patients with advanced metastatic pancreatic cancer expressing PSCA were treated with escalating doses of BPX-601 cells in a 3+3 design. Nine of 12 patients received a single dose of rimiducid following BPX-601 treatment to evaluate its effect on cell expansion and persistence. Patients in the study received a reduced conditioning regimen consisting of cyclophosphamide only.

Interim Results:

The administration of BPX-601 without rimiducid resulted in limited expansion of cells, but the cells did not persist; A single dose of rimiducid 7 days following BPX-601 administration resulted in significant expansion of cells (three-fold to 20-fold) in four patients in spite of a reduced conditioning regimen; BPX-601 cells persisted longer than three weeks in three patients after a single dose of rimiducid; Increases in key cytokine levels were observed in patients receiving higher doses of BPX-601 cells and rimiducid; 4 of 6 efficacy-evaluable patients treated with BPX-601 and a single dose of rimiducid had stable disease, with two patients demonstrating tumor shrinkage greater than 20 percent; No cytokine release syndrome or neurotoxicity of any grade was reported; The most frequently observed AEs were consistent with those experienced by advanced cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies; Patients continue to be evaluated in the study.
"These results provide the first clinical evidence suggesting that our GoCAR-T technology drives expansion and persistence of therapeutic T cells in patients," said Rick Fair, President & CEO of Bellicum Pharmaceuticals. "We are excited about BPX-601 and the broader application of our technology intended to improve the safety and efficacy of cell therapies. With these promising results, we’re preparing to begin Part 2 of the BPX-601 study, adding patients with prostate and gastric cancers, allowing multiple doses of rimiducid and a more complete conditioning regimen. We’re looking forward to reporting updated results in 2019."

About BPX-601
BPX-601, the Company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence, and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for solid tumors expressing prostate stem cell antigen (PSCA), including pancreatic, prostate and gastric cancers.

On December 14, 2018 Pfizer Inc. (NYSE:PFE) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for ZIRABEV (bevacizumab), a potential biosimilar to Avastin (bevacizumab) (Press release, Pfizer, DEC 14, 2018, View Source [SID1234532063]).1 ZIRABEV is a monoclonal antibody for the treatment of metastatic carcinoma of the colon or rectum, metastatic breast cancer, unresectable advanced, metastatic or recurrent non-small cell lung cancer (NSCLC), advanced and/or metastatic renal cell cancer and persistent, recurrent or metastatic carcinoma of the cervix.2

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"If approved, ZIRABEV has the potential to expand access to this life-changing biologic cancer therapy for appropriate patients and healthcare professionals across Europe," said Joe McClellan, Vice President, Biosimilars Development at Pfizer. "Today’s positive CHMP opinion underscores Pfizer’s strong heritage in oncology and its ongoing commitment to bringing high-quality biosimilars to market, providing additional options for people living with certain cancers."

The regulatory submission is supported with a comprehensive data package and evidence demonstrating biosimilarity to the originator product. This includes results from the phase 3 REFLECTIONS B739-03 clinical comparative study, which demonstrated clinical equivalence and found no clinically meaningful differences between ZIRABEV and Avastin in patients with advanced non-squamous NSCLC.3 As part of the overall REFLECTIONS clinical trial program, ZIRABEV has been studied in approximately 400 subjects.3,4

ZIRABEV is Pfizer’s second therapeutic oncology biosimilar to receive a positive CHMP opinion from the EMA in 2018.5 Pfizer has a robust portfolio of potential biosimilar candidates in mid to late stage development and we are confident about our ability to bring these important medicines to the patients who need them around the world.6

On December 14, 2018 Idera Pharmaceuticals, Inc. (NASDAQ: IDRA) reported is presenting data from the ongoing phase 2 expansion of the ILLUMINATE-204 trial investigating tilsotolimod, Idera’s intratumorally-delivered toll-like receptor 9 (TLR9) agonist, in combination with ipilimumab (Yervoy*) (Press release, Idera Pharmaceuticals, DEC 14, 2018, View Source [SID1234532066]).

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ILLUMINATE-204 Key Findings:

37 patients dosed with 8 mg of tilsotolimod in combination with ipilimumab were evaluated for this update:
34 patients were evaluable for efficacy
All patients were evaluable for safety
Accrual is ongoing, with an additional 4 patients dosed
Responses, including 2 Complete Responses (CR), were observed in 11 of the 34 evaluable patients (32.4%)
Duration of response ranges from > 1 month to > 30 months, with 36% of responses ongoing
Per RECIST v1.1, the Overall Response Rate (ORR) is 29.4%; one patient with an unconfirmed Partial Response (uPR) at the end of treatment assessment progressed due to a new lesion at the 3-month follow-up disease assessment
Overall, 26 patients out of 34 evaluable for efficacy (76.5%) experienced disease control (CR, PR, or Stable Disease (SD))
Analysis of spider plots show tumor shrinkage in both injected and uninjected lesions, indicating an abscopal effect
Responding subjects include one patient with mucosal melanoma and one patient with acral melanoma, two forms of melanoma that are particularly difficult to treat
Importantly, 2 of 5 patients with prior ipilimumab experience achieved responses, further demonstrating a signal that tilsotolimod has the potential to help overcome prior ipilimumab resistance
The combination regimen continues to be generally well tolerated. 9/37 subjects (24.3%) had immune-related toxicities indicating that tilsotolimod + ipilimumab does not appear to add immune-related toxicity versus ipilimumab alone
Injection-related toxicities were grade 1-2 transient fever and flu-like symptoms lasting <48 hours
Additionally:

A RECIST v1.1 PR of > 2.5 years is ongoing in 1 patient treated with tilsotolimod 4 mg in combination with ipilimumab; and
A RECIST v1.1 CR of > 1 year is ongoing in 1 patient treated with tilsotolimod 16 mg in combination with pembrolizumab.
"The results from this combination are among the most promising we have seen in this challenging population of metastatic melanoma patients who have not benefited from front-line immunotherapy," stated Douglas B. Johnson, M.D., Assistant Professor of Medicine, Clinical Director, Melanoma Research Program, Vanderbilt University Medical Center. "In addition to the response rate, observing over 76% of patients achieving disease control is impressive for such a difficult-to-treat patient population."

The ILLUMINATE-204 trial is comprised of two distinct patient populations, patients who are ipilimumab naïve (N=up to 40; Primary Efficacy Endpoint Population) and patients who have ipilimumab experience (N=up to 20; Secondary Efficacy Endpoint Population). Of the initial 34 patients evaluable for efficacy, evaluations 9 of 29 patients from the Primary Efficacy Endpoint Population and 2 of 5 patients from the Secondary Efficacy Endpoint Population achieved responses.

Indications of the specific mechanism of action for tilsotolimod were suggested in the clinical responses observed in patients whose tumor HLA-ABC RNA (MHC class I) expression was low at baseline. As recently articulated by Rodig, et al.1 robust MHC class I expression is required for anti-CTLA-4 activity. These findings suggest that combining tilsotolimod with ipilimumab may overcome this resistance mechanism and, therefore, enhance the overall response rate compared to that expected with ipilimumab alone.

"The continued positive results from this trial, a response rate substantially higher than expected with ipilimumab alone, and anti-tumor activity in both injected and uninjected lesions are exciting. These reinforce our conviction that tilsotolimod may overcome an immunosuppressive tumor microenvironment and, in combination with ipilimumab, could provide a treatment option when anti PD-1 therapy fails these patients," stated Dr. Joanna Horobin, Idera’s Chief Medical Officer. "These data, along with the translational data, bolster our confidence in both the Phase 3 trial and taking tilsotolimod beyond melanoma."

Investor Event and Webcast
Idera will host a conference call and live webcast today, Friday, December 14, at 10:00 A.M. EST to review the data being presented along with questions and answers. To participate in the conference call, please dial (844) 882-7837 (domestic) and (574) 990-9824 (international). The webcast can be accessed live or in archived form in the "Investors" section of the company’s website at www.iderapharma.com. The company has posted a slide presentation to the Idera corporate website in the "Investors" section which will be referenced during the conference call this morning.

About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the tumor-specific T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About ILLUMINATE-204
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda** (pembrolizumab) or Opdivo* (nivolumab) has failed. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy) or pembrolizumab (Keytruda) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.

For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.

About Metastatic Melanoma
Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.