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CBMG Responds to Inquiries from Investors and the Scientific Community About the Phase IIa Results from CAR-T CD20 Immuno-Oncology Clinical Development Program for Advanced B-cell Non-Hodgkin Lymphoma

On November 3, 2015 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biomedicine firm engaged in the development of effective treatments for degenerative and cancerous diseases, reported that it has responded to inquiries from investors and the scientific community about the announced results from an ongoing Phase IIa clinical trial evaluating the safety, feasibility and anti-tumor activity of its acquired Chimeric Antigen Receptor-Modified T-Cells (CAR-T) immunotherapy (CBM-CD20.1) targeting CD20 for the treatment of patients with advanced B-cell Non-Hodgkin lymphoma (NHL) (Press release, Cellular Biomedicine Group, NOV 3, 2015, View Source [SID:1234507920]).

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What are the significant treatment differences between the Phase I and Phase IIa studies?
The Phase IIa study excluded patients with uncontrolled bulky lymphoma (maximum diameter ≥5 cm or lesion number >3) after salvage treatments. The object of the early Phase IIa study is to evaluate the clinical activity of CBM-CD20.1 in NHL patients refractory or relapsed after chemotherapy. We also want to evaluate whether CBM-CD20.1 might improve the clinical outcome of advanced NHL patients that respond partially to chemotherapy. There will be a more detailed discussion in an upcoming manuscript in a peer-reviewed journal.

Please clarify how many patients actually enrolled in this Phase IIa NHL trial?
Fifteen patients were screened and twelve patients were enrolled. Of the twelve patients enrolled, two patients did not proceed with cell infusion. One withdrew consent and the other had disease progression and did not meet the inclusion criteria. Nine of the ten patients were refractory or relapsed after chemotherapy. The tenth patient showed partial response to most recent chemotherapy.

The abstract published by the 4th International Conference on Translational Medicine held in Baltimore on October 26-28th discussed an 11th patient from the Phase I trial. This patient remained in complete remission for over 25 months since the initial treatment of CBM-CD20.1, and the response is still on going. This patient was given a second treatment of CBM-CD20.1 infusions at 16 months post initial treatment based on the significant decrease of CD20 CAR-T cells in the peripheral blood ("Patient X"). In congruence with study protocol, we did not include Patient X in our presentation. The presented data of the 10 patients (seven patients with diffuse large B-cell lymphoma (DLBCL) and three patients with other types of NHL) from the Phase IIa trial can be viewed on the Company website under Investor Relations/Presentations.

How many of the patients who participated in the original Phase I trial enrolled in the Phase IIa study?None of the ten patients reported in the Company’s October 28th press release had participated in the original Phase I trial.

Please provide rationale on why the Phase II study result is substantially better than that of the Phase I study.
Besides excluding patients with uncontrolled bulky lymphoma, there were improvements in the conditioning regimen and treatment protocol, as well as the CBM-CD20.1 CART production process. Together these contributed to the improved clinical outcome in the phase IIa results.

What is the Company’s next step on targeting CD20 for the treatment of NHL?
The company intends to seek an opportunity to confirm the safety and clinical efficacy of CBM-CD20.1 in advanced NHL in a multicenter, single arm, Phase IIb trial. We plan to also explore other opportunities such as repeated treatment of CBM-CD20.1 or combination with other immuno-oncology therapies in advanced NHL.

Bristol-Myers Squibb and the Johns Hopkins Kimmel Cancer Center Enter Into a Collaboration Agreement as Part of U.S. Immuno-Oncology Rare Population Malignancy Research Program

On November 3, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported that they have entered into a collaboration agreement with The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins as part of Bristol-Myers Squibb’s Immuno-Oncology Rare Population Malignancy (I-O RPM) program in the U.S (Press release, Bristol-Myers Squibb, NOV 3, 2015, View Source [SID:1234507919]). The I-O RPM research program is a multi-institutional initiative with academic-based cancer centers focused on the clinical investigation of immuno-oncology therapeutics as potential treatment options for patients with high risk, poor prognostic cancers, defined as a rare population malignancy.

As part of the I-O RPM program, Bristol-Myers Squibb and the Johns Hopkins Kimmel Cancer Center will conduct a range of early phase clinical studies and Bristol-Myers Squibb will fund positions within The Johns Hopkins University School of Medicine fellowship program.

"Johns Hopkins has been a long-time collaborator with Bristol-Myers Squibb in immuno-oncology research," said Laura Bessen, M.D., head of U.S. Medical, Bristol-Myers Squibb. "We look forward to working with them as part of the I-O RPM research program as we continue to advance the science in this innovative field of cancer research and development, particularly among subpopulations of patients with high risk, poor prognostic cancers."

About I-O RPM

Immuno-oncology is an innovative approach to cancer research and treatment that is designed to harness the body’s own immune system to fight cancer. The I-O RPM research program focuses on significant areas of high unmet need marked by poor outcomes among patients with rare population malignancies. A rare population malignancy is a subpopulation within a higher incident disease population. These patients have aggressive disease with an increased potential for early metastasis to multiple sites and/or are initially refractory or subject to early recurrences with conventional cancer therapies. Existing clinical research provide a strong rationale for further research into the potential of immunotherapies for these cancers.

The I-O RPM research program is a multi-institutional initiative with Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Northwestern Medicine Developmental Therapeutics Institute, Moffitt Cancer Center and now the Johns Hopkins Kimmel Cancer Center. I-O RPM builds on Bristol-Myers Squibb’s formation in 2012 of the International Immuno-Oncology Network (II-ON), which is a global collaboration between Bristol-Myers Squibb and academia focused on facilitating the translation of scientific research findings into clinical trials and, eventually, clinical practice.

Threshold Pharmaceuticals Announces Preclinical Data on Combination of Evofosfamide With Immune Checkpoint Inhibitors to Be Presented at the SITC 2015 Meeting

On November 3, 2015 Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) reported that preclinical data on the combination of evofosfamide with immune checkpoint inhibitors will be presented in a scientific poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in Maryland, November 4-8, 2015 (Press release, Threshold Pharmaceuticals, NOV 3, 2015, View Source [SID:1234507918]). Evofosfamide is Threshold’s investigational hypoxia-activated prodrug, which is currently the subject of two fully-enrolled Phase 3 clinical trials for which Threshold expects to announce top-line data around the end of 2015.

"This is an exciting time for the field of cancer immunotherapy, and continued progress will depend on a better understanding of the tumor microenvironment and finding novel combination therapies that are more effective than immunotherapy alone," said Michael A. Curran, Ph.D., Assistant Professor at the University of Texas M.D. Anderson Cancer Center and senior author on the scientific poster.

"Our research shows that hypoxia in the tumor microenvironment forms a barrier to T cell infiltration and fosters immunotherapy resistance in prostate cancer and other solid tumors," Curran said. "We found that evofosfamide-driven disruption of hypoxic zones sensitizes highly resistant prostate cancer models to treatment with immune checkpoint inhibitors anti-CTLA-4 and anti-PD-1."

Research conducted in Curran’s laboratory shows that hypoxic zones in prostate tumors resist infiltration by T cells, which are capable of attacking and killing tumor cells. In contrast, normoxic areas of the same tumor experience robust infiltration by T cells.

In mouse models of prostate cancer, Curran and colleagues show that combination therapy with evofosfamide and anti-CTLA-4/anti-PD-1 treatment opens up the hypoxic zones to T cell infiltration.

Furthermore, evofosfamide helps sensitize otherwise immunotherapy-resistant prostate tumors to anti-CTLA-4/anti-PD-1 therapy in models of prostate cancer as evidenced by the smallest tumor burdens on average being observed with combination therapy.

"This combination of hypoxia disruption and T cell checkpoint blockade has potential to render some of the most therapeutically resistant cancers sensitive to immunotherapy," Curran said.

"Combining with immunotherapy is an exciting possibility that fits well with our development strategy to maximize the potential therapeutic applications of evofosfamide," said Tillman Pearce, M.D., Chief Medical Officer at Threshold. "The data from Dr. Curran’s research suggests that combining evofosfamide with immune checkpoint inhibitors warrants further investigation."

The poster titled "Tumor hypoxia drives immune suppression and immunotherapy resistance" by Midan Ai et al. will be presented on Saturday, November 7, 2015, from 12:45 PM – 2:00 PM. The abstract is now available at View Source or by clicking here.

About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug that is thought to be activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. Evofosfamide is currently in two Phase 3 trials, both of which are fully recruited: one in combination with doxorubicin versus doxorubicin alone in patients with locally advanced unresectable or metastatic soft tissue sarcoma (STS) (the TH-CR-406 trial), and the other in combination with gemcitabine versus gemcitabine and placebo in patients with locally advanced unresectable or metastatic pancreatic cancer (the MAESTRO trial). Top-line data for both trials are expected around the end of 2015. Both Phase 3 trials are being conducted under Special Protocol Assessment (SPA) agreements with the FDA. The FDA and the European Commission have granted evofosfamide Orphan Drug designation for the treatment of STS and pancreatic cancer. The FDA has also granted Fast Track designation for evofosfamide for both STS and pancreatic cancer. Evofosfamide is also being investigated in a Phase 2 trial designed to support registration for the treatment of non-squamous non-small cell lung cancer, and in earlier-stage clinical trials of other solid tumors and hematological malignancies.

Threshold has a global license and co-development agreement for evofosfamide with Merck KGaA, Darmstadt, Germany, which includes an option for Threshold to co-commercialize in the U.S.

MabVax Therapeutics Completes Manufacturing of HuMab 5B1 for Upcoming Phase I Clinical Trials

On November 3, 2015 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX), a clinical-stage oncology drug development company, reported it has completed manufacturing of the bulk clinical-quality drug substance of HuMab 5B1 in preparation for the planned initiation of two Phase I clinical trials with this antibody in early 2016 (Press release, MabVax, NOV 3, 2015, View Source [SID:1234507911]). The bulk clinical material was manufactured under Good Manufacturing Practices (GMP), has cleared all testing and has been released to be packaged into finished product.

Paul Maffuid, Ph.D., Vice President of Development and Operations of MabVax, said, "We are pleased to have completed the manufacture of the first lot of GMP bulk drug substance which is a tribute to our staff and collaborators who aided in this effort. Production of finished drug product and the information generated during this campaign are essential components of our two Investigation New Drug (IND) submissions planned for later this year."

The first Phase I trial will evaluate the safety and utility of HuMab 5B1 as a therapeutic in subjects with metastatic pancreatic cancer as a single agent or in combination with the current standard-of-care chemotherapy regimen. The second Phase I trial will be aimed at demonstrating the utility of 89Zr-HuMab 5B1, a radiolabeled HuMab 5B1 antibody, as a next-generation PET imaging agent for the identification, imaging and monitoring of pancreatic cancer.

"We believe the safety and targeting specificity data generated in the early portions of these two Phase I trials will validate the utility of the HuMab 5B1 antibody in this devastating disease," said MabVax’s President and Chief Executive Officer David Hansen. "We are excited about the potential applicability of our dual-product development approach in other cancers with HuMab 5B1, as well as with follow-on antibodies under development at MabVax."

About HuMab 5B:

In preclinical research MabVax’s HuMab 5B1 antibody has demonstrated high specificity, affinity and lack of cross-reactivity with closely related antigens. The antibody has also shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon and small cell lung cancer. When combined with a radio-label as a novel PET imaging agent, 89Zr-HuMab 5B1 has demonstrated high image resolution of tumors in established xenograft animal models, making it attractive as a companion diagnostic for the therapeutic product.

Epacadostat in Combination with Pembrolizumab Demonstrates Promising Clinical Activity in Multiple Advanced Cancers

On November 3, 2015 Incyte Corporation (Nasdaq:INCY) reported the first presentation of findings from the ongoing proof-of-concept Phase 1/2 study evaluating epacadostat, Incyte’s selective IDO1 inhibitor, in combination with pembrolizumab, an anti-PD-1 therapy (Press release, Incyte, NOV 3, 2015, View Source [SID:1234507910]). Results evaluating 19 patients for efficacy and 28 patients for safety, indicate a 79 percent (n=15/19) disease control rate (DCR) in evaluable patients with advanced cancers. Responses were observed in all tumor types assessed. In the melanoma group (n=7), four of seven patients treated with the combination of epacadostat and pembrolizumab had an objective response, including 2 complete responses (CRs), with disease control demonstrated in six of the seven patients treated with the combination.

These results (see Appendix) will be published in the Journal for ImmunoTherapy of Cancer on November 4, 2015. Updated study results—including safety data on 56 patients and efficacy data on 47 patients, inclusive of 19 evaluable melanoma patients—will be presented by Dr. Tara Gangadhar as a late-breaking oral presentation (Abstract #142) on Friday, November 6, 2015 from 12:00-12:15 PM EST at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 30th Anniversary Annual Meeting & Associated Programs. Following the presentation, the updated data will be made available on www.incyte.com.

"These new data underscore the potential of epacadostat to treat advanced forms of cancer when used in combination with an anti-PD-1 therapy," said Rich Levy, MD, Chief Drug Development Officer of Incyte. "We look forward to further evaluating the clinical benefits of the combination of epacadostat and pembrolizumab, both within the planned Phase 3 melanoma study that is expected to begin in the first half of next year, and in other future clinical programs."

About the Study

The ongoing dose-escalation and dose-expansion study of epacadostat in combination with pembrolizumab includes patients with advanced melanoma, renal cell carcinoma (RCC), transitional cell carcinoma (TCC), non-small cell lung cancer (NSCLC), endometrial adenocarcinoma (EA), or squamous cell carcinoma of the head and neck (SCCHN). Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded.

Study Results

Overall Response Rates (ORR) and Disease Control Rates (DCR) in Advanced Cancers

Adverse events (AEs) included a DLT (grade 3 rash) observed in 1/8 patients with epacadostat 50 mg BID/pembrolizumab 2 mg/kg; no DLTs were observed with epacadostat 100 mg BID/pembrolizumab 2 mg/kg. The most common (≥20%) all grade AEs were fatigue, diarrhea, rash, arthralgia, and nausea; the majority of these were grade 1 or 2. Grade ≥3 immune-related AEs were mucosal inflammation and rash (n=1 [4%] each).

Correlations between biomarker expression and response are being evaluated, and enrollment in expansion cohorts is ongoing.

These data will be discussed as part of Incyte’s previously arranged third quarter 2015 financial results conference call and webcast at 10:00 AM ET on Tuesday, November 3, 2015.

About Epacadostat

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity.

Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer histologies. A Phase 3 study evaluating the combination of epacadostat with pembrolizumab as first-line treatment for patients with advanced or metastatic melanoma is expected to begin in the first half of 2016.