NWBO Northwest Biotherapeutics Inc (QB)

 

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SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

 

FORM 8-K

 

CURRENT REPORT PURSUANT TO SECTION 13 OR 15(D) OF

THE SECURITIES EXCHANGE ACT OF 1934

 

 

Date of report (Date of earliest event reported)

March 26, 2015

 

NORTHWEST BIOTHERAPEUTICS, INC.

(Exact Name of Registrant as Specified in Its Charter)

 

Delaware	0-33393	94-3306718
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(I.R.S. Employer Identification No.)
4800 Montgomery Lane, Suite 800, Bethesda, MD 20814 (Address Of Principal Executive Offices) (Zip Code)

 

(204) 497-9024

(Registrant's Telephone Number, Including Area Code)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

¨	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
¨	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
¨	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
¨	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

 

Item 7.01. Regulation FD Disclosure.

 

On March 26, 2015, representatives of Northwest Biotherapeutics, Inc. (the “Company”) presented certain clinical data at the 2nd Immunotherapy of Cancer Conference, held in Munich, Germany. On March 27, the Company issued a press release summarizing the clinical data that were presented at the conference. Filed herewith as Exhibit 99.1 is the March 27 press release. Filed herewith as Exhibit 99.2 and 99.3 are the poster presentation and slides that were presented at the conference. The press release, poster presentation, slides and other information, including a webcast link, are also available on the Company's website at www.nwbio.com.

 

Item 9.01. Financial Statements and Exhibits.

 

Exhibit Number	Description
99.1	Press Release dated March 27, 2015.
99.2	Poster presented at 2nd Immunotherapy of Cancer Conference
99.3	Slides presented at 2nd Immunotherapy of Cancer Conference

 

 

SIGNATURES

 

PURSUANT TO THE REQUIREMENTS OF THE SECURITIES EXCHANGE ACT OF 1934, THE REGISTRANT HAS DULY CAUSED THIS REPORT TO BE SIGNED ON ITS BEHALF BY THE UNDERSIGNED THEREUNTO DULY AUTHORIZED.

 

	NORTHWEST BIOTHERAPEUTICS, INC.
Date: March 27, 2015	By:	/s/ Linda Powers
		Linda Powers, Chief Executive Officer, Chairperson

 

 

 

Exhibit 99.1

 

	Northwest	t (240) 497-9024	www.nwbio.com
	Biotherapeutics, Inc.	f (240) 627-4121	NASDAQ:NWBO
	4800 Montgomery Lane
	Suite 800
	Bethesda, MD 20814

 

NW BIO REPORTS PROMISING SURVIVAL DATA

 

IN 51 GBM PATIENTS TREATED WITH DCVAX®-L

 

Patients Too Sick for Enrollment in Phase III Trial for Newly Diagnosed GBM

 

BETHESDA, MD, March 27, 2015 - Northwest Biotherapeutics, Inc. (NASDAQ: NWBO) (“NW Bio”), a biotechnology company developing DCVax® personalized immune therapies for cancer, announced today that Dr. Marnix Bosch, the Company’s Chief Technical Officer, presented encouraging survival data on 51 Glioblastoma multiforme (GBM) brain cancer patients treated with DCVax®-L. The data showed substantially longer than expected survival in patients with apparent early progression (recurrence) of their cancer, including patients with such aggressive cancer that the tumor was already re-growing by the end of 6 weeks of daily radiotherapy and chemotherapy after surgical removal of the original tumor.

 

As previously announced, Dr. Bosch’s presentation was made at the 2^nd Immunotherapy of Cancer (ITOC) Conference in Munich, Germany, yesterday and was webcast. The webcast of the presentation, entitled “Prolonged Survival In Patients With Recurrent GBM Who Are Treated With Tumor Lysate-Pulsed Autologous Dendritic Cells,” can be seen for up to 30 days at http://nwbio.com/webcasts/ The presentation poster can be found on the Company’s website.

 

The 51 GBM patients were treated in an Information Arm outside the Company’s Phase III clinical trial because they were not eligible for the trial, due to evidence of early tumor re-growth following 6 weeks of daily radiotherapy and chemotherapy which are standard of care. Overall Survival data is available for all 51 patients; however, MRI images are only available for 46 of the 51 patients. These 46 patients were classified by an independent medical imaging company into 3 groups, as follows. The other 5 patients remained unclassified, due to lack of available images.

 

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20 Rapid-Progressor Patients: Patients with a new lesion ≥ 1 cm. in size, or tumor growth of ≥25% both at a Baseline Visit and at Month 2 thereafter;

 

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25 Indeterminate Patients: Patients with evidence of progression at the Baseline Visit (rendering them ineligible for the trial), followed by stable disease, modest progression and/or modest regression (or unclear tumor measurements), neither of which is enough to classify them as either a Rapid-Progressor or a Pseudo-Progressor;

 

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1 Pseudo-Progressor: A patient whose Month 2 image showed resolution of most of the prior appearance of tumor growth that had been seen at the Baseline Visit.

 

 

The prognosis for Rapid Progressor patients is especially poor: their median Overall Survival is only about 8 to 10 months, according to published scientific literature, and they generally are not expected to respond much to any treatments. There is no established benchmark for Overall Survival of the Indeterminate Patients, however, they can be compared to the general population of GBM patients, for whom median Overall Survival is 14.6 months.

 

The survival to date, for each of these groups of Information Arm patients treated with DCVax-L, is as follows:

 

·

Overall: The median OS of the group of 51 Information Arm patients as a whole is 18.3 months. About 30% of the patients (15 of the 51) lived beyond 2 years, and most of these patients (12 of the 15) remain alive.

 

·

20 Rapid-Progressors: The median OS among these 20 DCVax-L treated patients is 15.3 months (with patients surviving as long as 37.1 months), compared to expected median OS of 8.3 - 10.8 months with existing treatments, based on published literature on comparable patient populations -- a 50% improvement over the expected survival time. Further, one-third of these patients (7 of the 20) lived beyond 18 months – a doubling of the expected survival time with existing treatments.

 

·

25 Indeterminate Patients: The median OS among these DCVax-L treated patients is 21.5 months (with patients surviving as long as 40.7 months), compared to median OS in the general population of newly diagnosed GBM patients of 14.6 months – a 50% improvement over the expected survival time. Further, 9 of these 25 patients remain alive today at more than 24 months, 6 of these 9 patients have exceeded 30 months, and 4 of these 9 patients have reached 35-40+ months.

 

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1 Pseudo-Progressor: This patient is still alive, with OS of 30.1 months to date.

 

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5 Unclassified Patients: The median OS is 9.2 months (with patients surviving as long as 30.1 months).

 

As reflected in these data, both Rapid-Progressor Patients and Indeterminate Patients (as well as the Pseudo-Progressor Patient) treated with DCVax-L in the Company’s Information Arm are surviving substantially longer than would be expected based on clinical experience reported in the literature.

 

DCVax-L also continues to show an excellent safety profile, with no serious adverse events observed in these Information Arm patients.

 

“We are quite encouraged to see survival times in our DCVax-L treated Information Arm patients that exceed the expected survival times with existing treatments by 50% or more” commented Linda Powers, CEO of NW Bio. “This survival data, which has been collected by the independent CRO managing our Phase III trial, provides an encouraging insight into the potential results of the DCVax-L treatments for newly diagnosed patients in the Phase III trial. The survival data also reinforce the results we have seen with extended survival in our prior Phase I/II trials, and reinforce NW Bio’s position as a leader in immune therapies for cancer.”

 

 

Background

 

The Company treated a total of 55 patients in an “Information Arm” outside of the Company’s ongoing Phase III clinical trial of DCVax-L for newly diagnosed GBM: 51 of these 55 patients were not eligible for the trial because they had evidence of early progression (tumor growth) at a Baseline Visit at the end of 6 weeks of daily radiotherapy and chemotherapy after surgical resection of their brain tumor; 4 of the patients were not eligible for the trial for other reasons (e.g., insufficient doses of DCVax-L).

 

These Information Arm patients received the same DCVax-L product, on the same treatment schedule, in the same medical centers, in the same time period as the Phase III clinical trial, and the data have been collected and maintained by the same contract research organization (CRO) managing the Phase III trial.

 

As Dr. Bosch described in his conference presentation, as part of the eligibility assessment for the Phase III clinical trial, patients underwent MRI imaging at a Baseline Visit at the end of the 6 weeks of daily radiotherapy and chemotherapy which is standard of care following the surgical removal of the original tumor. Patients who already have disease progression (tumor re-growth) so quickly, and in the midst of such daily treatments, are generally considered to be “Rapid Progressors.” Such patients are usually excluded or segregated in studies and analyses because their disease is so accelerated that it is not comparable to regular GBM patients.

 

The patients in NW Bio’s Information Arm were evaluated through MRI imaging at the Baseline Visit and at Month 2 thereafter. All images were reviewed and analyzed by an independent specialized medical imaging company. Each image was reviewed separately by two independent reviewers, and any material differences were resolved by a third independent reviewer. Reviews were conducted using both RANO and McDonald criteria.

 

About Northwest Biotherapeutics

 

Northwest Biotherapeutics is a biotechnology company focused on developing immunotherapy products to treat cancers more effectively than current treatments, without toxicities of the kind associated with chemotherapies, and on a cost-effective basis, in both the United States and Europe.  The Company has a broad platform technology for DCVax dendritic cell-based vaccines.  The Company’s lead program is a 348-patient Phase III trial in newly diagnosed Glioblastoma multiforme (GBM).  GBM is the most aggressive and lethal form of brain cancer, and is an “orphan disease.”  The Company is under way with a 60-patient Phase I/II trial with DCVax-Direct for all inoperable solid tumors cancers, with a primary efficacy endpoint of tumor regression.  It has completed enrollment in the Phase I portion of the trial.  The Company previously received clearance from the FDA for a 612-patient Phase III trial in prostate cancer.  The Company conducted a Phase I/II trial with DCVax for metastatic ovarian cancer together with the University of Pennsylvania.  In Germany, the Company has received approval of a 5-year Hospital Exemption for the treatment of all gliomas (brain cancer) patients outside the clinical trial.

 

 

Disclaimer

 

Statements made in this news release that are not historical facts, including statements concerning future treatment of patients using DCVax and future clinical trials, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.  Words such as “expect,” “believe,” “intend,” “design,” “plan,” “continue,” “may,” “will,” “anticipate,” and similar expressions are intended to identify forward-looking statements.  Actual results may differ materially from those projected in any forward-looking statement.  Specifically, there are a number of important factors that could cause actual results to differ materially from those anticipated, such as risks related to the Company’s ongoing ability to raise additional capital, risks related to the Company’s ability to enroll patients in its clinical trials and complete the trials on a timely basis, uncertainties about the clinical trials process, uncertainties about the timely performance of third parties, risks related to whether the Company’s products will demonstrate safety and efficacy, risks related to the Company’s and Cognate’s abilities to carry out the intended manufacturing expansions contemplated in the Cognate Agreements, risks related to the Company’s ability to carry out the Hospital Exemption program and risks related to possible reimbursement and pricing.  Additional information on these and other factors, including Risk Factors, which could affect the Company’s results, is included in its Securities and Exchange Commission (“SEC”) filings.  Finally, there may be other factors not mentioned above or included in the Company’s SEC filings that may cause actual results to differ materially from those projected in any forward-looking statement.  You should not place undue reliance on any forward-looking statements.  The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by securities laws.

 

CONTACTS:

 

Les Goldman

202-841-7909

lgoldman@nwbio.com

 

Farrell Kramer (Media)

212-710-9685

Farrell.kramer@mbsvalue.com

 

Jane Searle (Investors)

212-710-9686

Jane.Searle@mbsvalue.com

 

 

 

Exhibit 99.2

 

Prolonged Survival In Patients With Recurrent Glioblastoma Multiforme Who Are Treated With Tumor Lysate - Pulsed Autologous Dendritic Cells Marnix L. Bosch 1 , Robert Prins 2 and Linda Liau 2 1 Northwest Biotherapeutics, Inc , and 2 University of California, Los Angeles, USA ABSTRACT Background : Recurrent Glioblastoma multiforme (rGBM) is a life threatening condition, with a mortality rate approaching 100 % . Overall survival (OS) in rGBM patients has not materially changed in the past several decades . We treated 55 rGBM patients with autologous dendritic cells pulsed with autologous tumor cell lysate ( DCVax ® - L ) in an “Information Arm” outside of our Phase III clinical trial . 51 of these 55 patients were not eligible for the trial because they had actual or apparent early progression (recurrence) at a Baseline Visit at the end of 6 weeks of daily radiotherapy and chemotherapy after surgical resection of their brain tumor . 4 of the patients were not eligible for the trial for other reasons (e . g . , insufficient doses of DCVax - L) . These rGBM patients received the same DCVax - L product, on the same treatment schedule, in the same medical centers, in the same time period as the Phase III clinical trial, and the data have been collected and maintained by the same CRO managing the Phase III trial . Aim : To provide compassionate use treatment and to determine OS of these rGBM patients treated with DCVax - L . Methods : Disease progression (recurrence) was determined through MRI imaging at the Baseline Visit and at Month 2 thereafter . All images were reviewed and analyzed by an independent specialized medical imaging company . Each image was reviewed separately by two independent reviewers, and any material differences were resolved by a third independent reviewer . Reviews were conducted using both RANO and McDonald criteria . OS data is available for all 51 patients . Baseline and Month 2 images are available so far for 46 of the 51 patients . Based on comparison of the Baseline and Month 2 images, the independent medical imaging company classified the 46 patients into the following 3 groups . The other 5 patients were unclassified, due to lack of available images . • 20 Rapid - Progressor Patients : A new lesion ≥ 1 cm or tumor growth ≥ 25 % at Baseline and at Month 2 • 25 Indeterminate Patients : S table disease, modest progression and/or regression, or measurements still unclear • 1 Pseudo - Progressor : Month 2 image showed resolution of most of the prior appearance of tumor growth Median Overall Survival (OS) in Rapid - Progressor Patients Reference Population Median OS DCVax - L (20 patients) Progressive disease (PD) post RT+chemo , and additional PD (>25%) 2 months later 15.3 months Brandes et al. 2008 ( 18 patients) PD at 4 weeks post RT+chemo , confirmed after 2 more tmz cycles 10.2 months Roldan et al. 2009 ( 10 patients) PD at 4 - 6 weeks post RT+chemo , confirmed after ≥1 more tmz cycle(s) 9.1 months Kang et al. 2010 (10 patients) PD at 2 consecutive scans post RT+chemo 10.8 Sanghera et al. 2010 ( 29 patients) PD at 2 consecutive scans within 8 weeks post RT+chemo 8.3 months Gunjur et al. 2011 ( 27 patients) PD at 2 consecutive scans within 3 months post RT+chemo , or clinical deterioration 10.4 months Linhares et al . 2013 ( 13 ) PD at 2 consecutive scans within 3 months post RT+chemo 9.0 months Results Overall : The median OS is 18 . 3 months . 15 of the 51 patients who were ineligible for the Phase III trial due to apparent early recurrence lived beyond 2 years, and 12 of the 15 remain alive . 20 Rapid - Progressors : The median OS is 15 . 3 months ( 95 % Confidence Interval : 10 . 5 – 17 . 2 ) and the range is 6 . 7 to 37 . 1 months . A literature search revealed 6 publications with comparable populations of patients (listed at left), which reported median OS of 8 . 3 to 10 . 8 months . 12 of the 20 DCVax - L treated Rapid - Progressors lived beyond 13 months ; 10 of the 20 DCVax - L treated Rapid - Progressors lived beyond 15 months ; and 7 of the 20 DCVax - L treated Rapid Progressors lived beyond 18 months . 25 Indeterminate Patients : The median OS is 21 . 5 months, and the range is 8 . 8 to 40 . 7 months . 9 of these 25 patients remain alive today at more than 24 months, 6 of these 9 patients remain alive at more than 30 months, and 4 of these 9 patients remain alive at 35 - 40 + months . 1 Pseudo - Progressor : This patient is still alive . OS is 30 . 1 months to date . 5 Unclassified Patients : 1 patient is still alive . The median OS is 9 . 2 months, and the range is 5 . 7 to 30 . 1 months . 0 5 10 15 20 25 30 35 40 Recurrent GBM Median OS 8.3 – 10.8 Months In Literature 20 Patients Months 20 Rapid - Progressor Patients : Median Overall Survival 15.3 Months (Data as of February 2015) Patients Still Alive 25 Indeterminate Patients: Median Overall Survival 21.5 Months (Data as of February 2015) 0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0 Months 25 Patients Patients Still Alive Newly diagnosed GBM Median OS 14.6 Months With Standard of Care N Engl J Med 352: 987 - 96 , 2005 1 Pseudo - Progressor Patient: Overall Survival To Date 30 Months (Data as of February 2015) 0 5 10 15 20 25 30 35 Months 1 Patient Patients Still Alive 5 Patients Unclassified Due to Lack of Images (Data as of February 2015) 0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 Months 5 Patients Patients Still Alive Information Arm 51 patients had evidence of apparent disease progression in imaging at Baseline Visit following 6 weeks’ chemo - radiation Patients re - imaged at Month 2 after Baseline Visit to confirm either actual disease progression or pseudo - progression (patients categorized by independent medical imaging company) 20 patients had further progression at Month 2: Rapid - Progressors 25 patients had stable disease or modest progression/regression or measurements unclear at Month 2: Indeterminate 1 patient had resolution at Month 2: Pseudo - progressor 5 patients Unclassified due to lack of images Conclusions • Patients with evidence of disease recurrence immediately following 6 weeks of daily radiotherapy and chemotherapy after surgical resection of their brain tumor appear to survive longer than would be expected based on data in the literature, when treated with DCVax - L. • The apparent extended survival of these patients is seen in both Rapid Progressor Patients and Indeterminate Patients (as well as the Pseudo - Progressor Patient). • The combined data suggest a possible survival benefit for patients with recurrent GBM conferred by the DCVax - L treatment. • The ~30% of survivors who have lived beyond 2 years may reflect long term tumor control. • DCVax - L treatment (vaccination of patients with autologous dendritic cells loaded with autologous tumor lysate antigens) also continues to have an excellent safety profile.

 

 

Exhibit 99.3

  

Autologous Dendritic Cell Therapy for Cancer 2 nd Immunotherapy of Cancer Conference, ITOC - 2 Munich, Germany March 26, 2015 Marnix L. Bosch, MBA, PhD Chief Technical Officer Northwest Biotherapeutics

Disclaimer Certain statements made in this presentation are “forward - looking statements” of NW Bio as defined by the Securities and Exchange Commission (“SEC”). All statements, other than statements of historical fact, included in this presentation that address activities, events or developments that NW Bio believes or anticipates will or may occur in the future are forward - looking statements. These statements are based on certain assumptions made based on experience, expected future developments and other factors NW Bio believes are appropriate in the circumstances. Such statements are subject to a number of assumptions, risks and uncertainties, many of which are beyond the control of NW Bio. Investors and others are cautioned that any such statements are not guarantees of future performance. These forward - looking statements could cause actual results and developments to differ materially from those expressed or implied in such statements, including our ability to raise funds for general corporate purposes and operations, including our clinical trials, the commercial feasibility and success of our technology, our ability to recruit qualified management and technical personnel, our ability to scale up the manufacturing of our product candidates for commercialization, the success of our clinical trials and our ability to obtain and maintain required regulatory approvals for our products. Furthermore, NW Bio does not intend (and is not obligated) to update publicly any forward - looking statements. The contents of this presentation should be considered in conjunction with the risk factors contained in NW Bio’s recent filings with the SEC, including its most recent Form 10K. This communication is neither an offer to sell nor a solicitation of an offer to buy any securities mentioned herein. This publication is confidential for the information of the addressee only and may not be reproduced in whole or in part; copies circulated, or disclosed to another party, without the prior written consent of Northwest Biotherapeutics (NW Bio) are strictly prohibited. 2

Glioblastoma Multiforme (GBM) • GBM, Stage IV glioma, presents a significant unmet medical need – Average time to recurrence approximately 7 months – Average time to death approximately 15 months • Standard of care, radiation therapy + temozolomide, was approved in 2005 for GBM • There is no life - extending treatment for GBM following recurrence • Average time to death from first recurrence is approximately 9 months 3

GBM – Standard Treatment and Progression 1. If possible, surgical removal of most of the tumor tissue 2. Chemo - radiation: six weeks of radiation therapy + concomitant temozolomide 3. Adjuvant temozolomide: ≥ 6 cycles of 5 days on, 23 days off 4. Following recurrence 1. NovoTTF device 2. BCNU/CCNU chemotherapy 3. Bevacizumab, mostly to combat symptoms • Disease progression is monitored through MRI imaging • Radiation necrosis and other artifacts following radiation can mask as progression and are known as pseudoprogression 4

DCVax - L: Introduction • DCVax - L is autologous dendritic cells (DC) pulsed with autologous tumor cell lysate – DC are the master cells of the immune system, and are required to induce an adaptive immune response – Tumor lysate provides the antigens against which the immune response will be directed • DCVax - L is injected into the skin, as an outpatient treatment: the DC migrate to the lymph nodes to activate anti - tumor T cells • DCVax - L treatment is administered in conjunction with standard of care therapies, such as chemo - radiation for newly diagnosed GBM • Early clinical data (UCLA) are encouraging in both newly diagnosed and recurrent GBM 5

DCVax - L Phase I/II Trials for Newly Diagnosed GBM • 20 newly diagnosed GBM; 14 recurrent GBM; 5 lower grade gliomas • Standard of care (surgery & 6 weeks radiation & chemo) + DCVax - L • Primary endpoint: safety; Secondary endpoint: p rogression f ree survival 6 Standard of Care* Matched Concurrent Controls** DCVax - L Progression (Tumor Recurrence) 6.9 mos 8.1 mos 2 years Overall Survival 14.6 mos 17 mos 3 years Long Tail of Survival 2 – 3% alive at 5 years To date: 33% alive >4 yrs 27% alive >6 yrs 2 pts alive >10 yrs ** matched for age, gender, Karnofsky score, extent of surgical resection, and same std of care treatment, at same hospital, in same time period * N Engl J Med 352: 987 - 96, 2005

7 International Phase III Trial With DCVax - L for GBM • 348 patient , randomized (2:1), double blind, placebo controlled Phase III trial ▪ Primary endpoint: PFS (progression free survival ) ▪ Secondary endpoints include OS (overall survival ) ▪ 3 DCVax - L treatments upfront (Day 0, 10, 20), then 3 boosters (months 2, 4, 8) then 4 treatments twice/year for maintenance phase (months 12, 18, 24, 30) • Newly diagnosed GBM; trial under way in both US, Europe & Canada • Trial Design Features ▪ 4 - month extension of PFS required to meet primary endpoint ▪ Trial powered to reach p value = 0.02 if 4 - month difference in PFS shown ▪ Trial also powered for secondary endpoint of Overall Survival ▪ Multiple sub - group analyses were prospectively included

Informational Arm open label, for patients with apparent PD post chemo - radiation 8 51 patients had evidence of apparent disease progression in imaging at Baseline Visit following 6 weeks’ chemo - radiation Patients re - imaged at Month 2 after Baseline Visit to confirm either actual disease progression or pseudo - progression (patients categorized by independent medical imaging review company) 20 patients had further progression at Month 2: Rapid - Progressors 25 patients had stable disease or modest progression/regression or measurements unclear at Month 2: Indeterminate 1 patient had resolution at Month 2: Pseudo - progressor 5 patients Unclassified due to lack of images

Informational Arm: Overall Results • Median overall survival for the 51 patients with evidence of disease progression post chemo - radiation = 18.3 months (range 6.7 to >40.7 months) – This compares favorably to 14.6 months mOS for newly diagnosed GBM patients receiving standard care • 15 of 51 patients (~30%) lived beyond 2 years • 12 of the 15 patients are still alive, with follow up times of 26.9 – 40.7 months 9

Rapid Progressors: Results • 20 patients are classified as rapid progressors based on progression on 2 consecutive scans • Literature data show expected survival times of 8 – 10 months for such patients • Median survival in rapid progressors in the DCVax - L Informational Arm is 15.3 months (range 6.7 to >37.1 ) 10 Study n Median Survival DCVax-L 20 15.3 months (Brandes et al., 2008) 18 10.2 months (Roldan et al., 2009) 10 9.1 months (Kang et al., 2011) 10 10.8 months (Sanghera et al., 2010) 29 8.3 months (Gunjur et al., 2011) 27 10.4 months (Linhares et al., 2013) 13 9.0 months

0 5 10 15 20 25 30 35 40 Recurrent GBM Median OS 8.3 – 10.8 Months In Literature 20 Patients Months 20 Rapid - Progressor Patients : Median Overall Survival 15.3 Months (Data as of February 2015) Patients Still Alive Patients Still Alive

Other Patients: Results • 25 Informational Arm patients classified as Indeterminate : i.e., they had stable disease, or modest progression/regression, or unclear measurements – mOS = 21.5 months – 9 patients are still alive, at 26.9 – 40.7 months • 1 Informational Arm patient classified as a Pseudo - Progressor: i.e., the appearance of tumor re - growth at the Baseline Visit had resolved by the Month 2 visit. – t his patient is still alive, at 30.1 months 12

25 Indeterminate Patients: Median Overall Survival 21.5 Months (Data as of February 2015) 0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 40.0 45.0 Months 25 Patients Patients Still Alive Std of Care for New GBM: 14.6 Months mOS N Engl J Med 352: 987 - 96 , 2005

0 5 10 15 20 25 30 35 5 Patients 1 Pseudo - Progressor Patient Overall Survival To Date 30 Months (Data as of February 2015) 0 5 10 15 20 25 30 35 Months 1 Patient Patients Still Alive 5 Patients Unclassified Due to Lack of Follow - Up Images (Data as of February 2015) Informational Arm: Other Patients Patients Still Alive Months

Conclusions • Patients with evidence of disease recurrence immediately following 6 weeks of daily radiotherapy and chemotherapy after surgical resection of their brain tumors appear to survive longer than would be expected based on data in the literature, when treated with DCVax - L. • The apparent extended survival of these patients is seen in both Rapid Progressor Patients and Indeterminate Patients (as well as the Pseudo - Progressor Patient). • The combined data suggest a possible survival benefit for patients with recurrent GBM conferred by the DCVax - L treatment. • The ~30% of survivors who have lived beyond 2 years may reflect long - term tumor control. • DCVax - L treatment (vaccination of patients with autologous dendritic cells loaded with autologous tumor lysate antigens) continues to have an excellent safety profile. 15