8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 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): April 7, 2016

 

 

ZIOPHARM Oncology, Inc.

(Exact Name of Registrant as Specified in Charter)

 

 

 

Delaware   001-33038   84-1475642

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

One First Avenue, Parris Building 34, Navy Yard Plaza

Boston, Massachusetts

  02129
(Address of Principal Executive Offices)   (Zip Code)

(617) 259-1970

(Registrant’s Telephone Number, including Area Code)

Not applicable

(Former Name or Former Address, if Changed Since Last Report)

 

 

Check the appropriate box below if the Form 8-K is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨ 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 April 7, 2016, ZIOPHARM Oncology, Inc., or the Company, will present the attached presentation at the Jefferies 2nd Annual Immuno-Oncology Summit in Boston, Massachusetts.

A copy of the above referenced presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K. This information, including the information contained in the presentation furnished as Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is not incorporated by reference into any of the Company’s filings, whether made before or after the date hereof, regardless of any general incorporation language in any such filing.

 

Item 9.01 Financial Statements and Exhibits

 

  (d) Exhibits

 

Exhibit

No.

  

Description

99.1    Presentation of the Company dated April 7, 2016

 

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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 hereunto duly authorized.

 

    ZIOPHARM Oncology, Inc.
    By:  

/s/ Kevin G. Lafond

Date: April 7, 2016     Name:   Kevin G. Lafond
    Title:   Vice President Finance, Chief Accounting Officer and Treasurer

 

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INDEX OF EXHIBITS

 

Exhibit

No.

  

Description

99.1    Presentation of the Company dated April 7, 2016

 

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EX-99.1

Exhibit 99.1

 

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Exhibit 99.1

ZIOPHARM

Jefferies Immuno-Oncology Summit

April 2016


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Forward-looking statements

This presentation contains certain forward-looking information about ZIOPHARM Oncology, Inc. that is intended to be covered by the safe harbor for “forward-looking statements” provided by the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as “may,” “will,” “could,” “expects,” “plans,” “anticipates,” and “believes.” These statements include, but are not limited to, statements regarding the progress, timing and results of preclinical and clinical trials involving the Company’s drug candidates, and the progress of the Company’s research and development programs. All of such statements are subject to certain risks and uncertainties, many of which are difficult to predict and generally beyond the control of the Company, that could cause actual results to differ materially from those expressed in, or implied by, the forward-looking statements. These risks and uncertainties include, but are not limited to: whether chimeric antigen receptor T cell (CAR T) approaches, Ad-RTS-IL-12, TCR and NK cell-based therapies, or any of our other therapeutic candidates will advance further in the pre-clinical or clinical trials process and whether and when, if at all, they will receive final approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies and for which indications; whether chimeric antigen receptor T cell (CAR T) approaches, Ad-RTS-IL-12, TCR and NK cell-based therapies, and our other therapeutic products will be successfully marketed if approved; the strength and enforceability of our intellectual property rights; competition from other pharmaceutical and biotechnology companies; and the other risk factors contained in our periodic and interim SEC reports filed from time to time with the Securities and Exchange Commission, including but not limited to, our Annual Report on Form 10-K for the fiscal year ended December 31, 2015. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof, and we do not undertake any obligation to revise and disseminate forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events.

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Partnerships to implement multiple immunotherapies

Clinical Collaborators

Rapid Clinical Development

CAR-T Collaboration DNA Engine & Research (via Intrexon)

Biopharmaceutical PBL and IL-12 business of Merck KGaA, (via Intrexon) Darmstadt, Germany

Laurence Cooper, MD, PhD

Named CEO in May 2015

Developed Sleeping Beauty

technology in-licensed by

ZIOP/XON in Jan 2015

Previously professor

pediatric oncology at MD

Anderson Cancer Center:

expertise in immunotherapy,

led bone marrow transplant

program

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Technologies to execute tumor cells

Technologies

Cytokines Switches

Cellular templates

Safe targets Reduce burden on manufacturing Infuse T cells that maintain their replicative potential

Combinations

Co-infuse T cells with multiple specificities

Combine introduced immuno-receptor with cytokine Add conditional and induced expression Combine genetic insertion with genetic editing

Combine cell therapy with other immunotherapies

Neoantigens

Target driver mutations expressed exclusively within a patient’s tumor

Overcome the time to generate the T-cell products Overcome cost

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Platforms to products

Patient-derived platforms

Autologous

Myeloid T cell malignancies

Lentivirus

B-cell malignancies

Sleeping

Beauty T cell I Neo-antigen 1 T cell 2 Neo-antigen 2 T cell 3 Neo-antigen 3

Antigens known

Understanding targets and delivering immunotherapies

Off-the-shelf platforms Allogeneic (off-the-shelf)

Myeloid malignancies

Glioblastoma

Breast cancer

Donor

not be known

Recipients

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NK cell Adenovirus Antigens need


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Bio-engineering and bio-processing

Implementing manufacturing processes for both autologous and allogeneic settings RTS® and switches will address off-target effects, especially in solid tumors Continued optimization of manufacturing process to improve performance

– Shortened manufacturing of CAR T cells shows superior in vivo activity

Leveraging manufacturing through

– MDACC

– CMOs

Patient-derived (autologous)

Infusion Real time

NK T cells cells

Shorten manufacturing time to produce T or NK cells

Off-the-shelf (allogeneic)

In advance

NK T

cells Infusions cells

Match one donor with multiple recipients. Generate large numbers of T or NK cells with retained capacity to proliferate.

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Addressing unmet medical needs: pipeline

Preclinical Phase I Phase II

Ad-RTS-IL-12 GBM    

Breast Cancer    

Pediatric    

GBM + Checkpoint    

CAR    

CD19 1st Generation Leukemia/Lymphoma    

CD19 2nd Generation    

CD19 3rd Generation with cytokine    

Myeloid malignancies target Undisclosed    

Merck Target 1 Undisclosed    

Merck Target 2 Undisclosed    

Off-the-shelf myeloid malignancies target Undisclosed    

NK Cells    

Primary NK cells AML    

Combination with Ad-RTS-IL-12 Brain Cancer    

Genetically-engineered TBD    

TCR    Target 2016

Sleeping Beauty TCR TBD    

Target 2017

Sleeping Beauty TCR and cytokine TBD    

Other    

Regulatory T Cells GvHD

Modified Bacteria (microbiome) GvHD

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Ad-RTS-IL-12 + veledimex

Oral Activator Ad-RTS-hiL-12 Oral Activator Distant Tumors Cytotoxic Response Lymphatics IL-12 IFNg APC CD8+ CD4+

Next Steps

Combination therapy with checkpoint inhibitors

Pre-clinical data demonstrates improved

anti-tumor response in mice with glioma

Abstract at ASGCT May 2016

*As of Dec 15, 2015 Updated data at ASGCT 2016

Early brain tumor data encouraging (N=7)*

Patients enrolled at multiple centers Biomarkers supportive of activity Neurotoxicity minimal and manageable

“On-target toxicities” as expected and promptly reversible upon stopping veledimex

Early breast cancer data encouraging (N=6)*

First patient achieved 12 week PFS endpoint

Patient accrual accelerating with 5 patients enrolled during 4th quarter Looking for confirmation of increased memory T cells as seen in previous trials

“On-target toxicities” as expected and promptly reversible upon stopping veledimex

Updated data for both studies at ASCO 2016

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T cells genetically modified with tumor-specific CAR or TCRs

Golgi

Effector Effector functions functions

ER

Proteosome

CAR TCR

Antigen Co-signal

T cell T cell

Tumor

Transposon DNA plasmid IR/DR IR/DR CAR hEF1

Transposase DNA plasmid (or in vitro transcribed mRNA) CMVIE SB11 Transposase Co-delivery into cells by nucleofection

Transposase Transposon CAR Nucleus Cytoplasm “The Sleeping Beauty transposon-transposase system represents a unique non-viral system for introducing genes encoding T-cell receptors and chimeric antigen receptors into lymphocytes that can be of great value in the development of personalized immunotherapies for patients with cancer.”

Steven A. Rosenberg M.D., Ph.D. December 2015

Advantages of Sleeping Beauty non-viral platform:

Provides conduit to targeting solid tumor neo-antigens using T-

cell receptors

Lowers the cost of generating genetically modified T cells

Has the potential to generate T cells with minimal ex vivo

processing

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Sleeping Beauty: First-in-human study

Long term follow-up data from 1st generation Sleeping Beauty platform in two trials infusing CAR+ T cells after hematopoietic stem-cell transplantation (HSCT)

Showed favorable PFS and OS trends in both autologous and allogeneic cohorts

Non-viral Sleeping Beauty T-cell survival compared favorably versus viral approaches    

Historical Controls

Sleeping Beauty

Autologous HSCT

Recipient 49% 3-year PFS reported for patients with advanced DLBL

Recipient Donor Allogeneic HSCT 20 to 34% 1-year Os reported for patients with advanced ALL

Autologous HSCT & CD19-specific CAR+T cells 83% 3-year PFS for patients with DLBL SB-modified CAR+T cells Allogeneic HSCT & CD19-specific CAR+T cells 63% 1-year Os for patients with ALL

SB-modified CAR+T cells

Sleeping Beauty T Cell survival averaged 201 days; max 360 days

Sleeping Beauty T Cell survival averaged 51 days; max 180 days

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Intrexon/Merck KGaA, Darmstadt, Germany in CAR-T

Exclusive agreement to develop and commercialize CAR-T cancer therapies 2 novel CAR T targets nominated

Merck KGaA, Darmstadt, Germany to lead IND filing and pre-IND interactions, clinical development and commercialization Intrexon and ZIOPHARM retain ability to explore targets independently, granting Merck KGaA opt-in rights during clinical development Economics divided evenly between ZIOPHARM and Intrexon

$413 million per product in milestones

Tiered royalties up to lower-double digits on net sales

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Natural Killer Cells: Beyond CAR+ T cells

Natural killer (NK) cells

– Target tumors, e.g., with loss or mismatch of HLA

– Killing is independent of a specific (known) target antigen

– Cytokines, e.g., IL-12 are “fuel” for NK cells

– Build on promising proof-of-principle trials ongoing at MDACC infusing autologous and allogeneic NK cells manufactured using feeder cells

Launching Phase 1 trials of off-the-shelf NK cells for AML and brain tumors in 2016 & 2017

OTS NK cells & Ad-RTS-IL12

OTS NK cells

AML L Brain Brain tumor tu or

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TCR: Targeting private somatic mutations (neo-antigens)

PERSPECTIVE nature medicine Prospects for gene-engineered T cell immunotherapy for solid cancers

Nat Med. 2016 Jan 6;22(1):26-36

Science. 2015 Apr 3;348(6230):62-8

Science. 2015 Apr 3;348(6230):69-74

Direct binding

CAR+ T cell

10% of proteins are on cell surface

Indirect binding

TCR+ T cell

90% of proteins are within a cell

“Clinical evidence supports the hypothesis that immunogenic products of somatic mutations unique to each patient’s cancer—so-called neoantigens—are the relevant targets for successful immunotherapies”

“Success for cell-based immunotherapies may come from the arduous task of targeting the unique set of mutations that cause each patient’s cancer”

“Presently, use of the Sleeping Beauty (SB) transposon / transposase system has advanced farthest in clinical development”

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Sleeping Beauty: farthest advanced in non-viral clinical development

Patient (recipient) Biopsy Sequence Peripheral blood Sequence Neo-antigens T cells T cells

T cells

Antigen presentation Co-culture T cells

T cells

T cells

T cells

T cells

TCRs Ex vivo gene transfer to TCR using Sleeping Beauty

Nucleofection SB11 TCR Transposase Transposon Retrovirus encoding TCR

Non-viral Sleeping

Viral delivery

Beauty

Target solid tumor Limited appeal for intracellular targeting multiple neo-antigens via multiple intracellular antigens via TCRs TCRs

Low cost approach High cost approach

Rapid Labor intensive, manufacture slow manufacture

Customizable, able to

Challenging to swap in different customize receptors

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Examples of neoantigen-specific TCRs to target solid tumors

Melanoma: AHNAKmut-TCR

AHNAKS2580F(A*0201)

Melanoma: ERBB2mut-TCR

ERBB2H473Y(A*0201)

Cholangiocarcinoma: ERBB2IPmut-TCR

ERBB2IPE805G(DQB*0601)

Molecular Therapy 05 March 2016

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Power-law curve

The industrialization of immunotherapies

Traditional Bio-pharma

Sleeping Beauty is critical to patients Cost of distribution achieving n=1 response at scale of Number Next-generation immune Bio-pharma 1

Number of trials

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Multiple immunotherapies and combination immunotherapies are being administered

Current Clinical Approaches leading to combination immunotherapy

Administer modified immune cells to Administer IL-12 via controlled gene therapy provide effective anti-tumor response to bolster endogenous immune response

T cells

CAR

T T

TCR

NK

NK Ad-RTS-IL-12 + veledimex

Cytokines NK cells

We stand alone in our ability to control the delivery of IL-12

We stand alone in being able to harness non-viral DNA as a method to genetically control T cells

We are launching multiple immunotherapy trials

Trial initiated with 2nd generation CD19 CAR-T utilizing non-viral Sleeping Beauty platform

Three new trials in 2016: Combination immunotherapy, viral CAR-T, and NK cells

We are combining different elements of the immune system

We have an ecosystem to efficiently develop and test new ideas in the clinic

We have an expanding and unique platform to control the immune system

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ZIOPHARM

Jefferies Immuno-Oncology Summit

April 2016