On August 9, 2016 Caladrius Biosciences, Inc. (NASDAQ: CLBS) ("Caladrius" or the "Company"), a cell therapy company combining an industry-leading development and manufacturing services provider through its subsidiary PCT, LLC a Caladrius Company ("PCT") with a select therapeutic development pipeline, reported financial results for the three and six months ended June 30, 2016 (Press release, Caladrius Biosciences, AUG 9, 2016, View Source [SID:1234514498]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Business highlights for the second quarter and recent weeks include:

•Achieved total revenues of $8.3 million for the second quarter of 2016, up 41% compared with $5.9 million in the second quarter of 2015;
•Achieved total operating costs and expenses reduction of 50% in the second quarter of 2016 when compared with the second quarter of 2015;
•Granted Fast Track designation from the U.S. Food and Drug Administration ("FDA") for CLBS03 for the treatment of recent onset type 1 diabetes mellitus ("T1D"), making it the first known therapeutic candidate to receive Fast Track designation for treatment of T1D;
•Granted Orphan Drug designation from the FDA for CLBS03 for the treatment of T1D with residual beta cell function;
•Expanded PCT’s relationship with Kiadis Pharma with an agreement for the manufacturing of their lead product, ATIR101, for the U.S. and Canadian Phase 3 trial in blood cancers;
•Announced the appointment of Robert A. Preti, Ph.D., the Company’s Chief Technology Officer, Senior Vice President, Manufacturing and Technical Operations, and President of PCT, as Chairman of the Alliance for Regenerative Medicine ("ARM"), the international advocacy organization representing the gene and cell therapies and broader regenerative medicine sector; and
•Licensed exclusive global rights to the Company’s tumor cell/dendritic cell technology for the treatment of ovarian cancer to AiVita Biomedical, Inc. In return, Caladrius will receive certain development milestone payments as well as royalties on sales.

Management Commentary

"We remain very pleased with our year-to-date performance as we continue to deliver on our strategic goals to grow and expand the PCT business, to reduce expenses, to advance our Phase 2 T-Rex clinical trial as a treatment for T1D and to monetize non-core assets," stated David J. Mazzo, Ph.D., Chief Executive Officer of Caladrius. "We are delighted to add Fast Track and Orphan Drug designations to CLBS03 for the treatment of T1D as they underscore the significant unmet medical need in this degenerative disease, and provide regulatory provisions that can accelerate the review process and expand our market exclusivity. We look forward to completing enrollment and treatment of the first cohort of approximately 18 patients toward the end of summer. Following the three-month post-treatment visit, an interim safety analysis will be conducted, and we expect to have these results by year-end 2016."

"We entered the second half of 2016 in a solid position to continue advancing our strategic goals and achieving our financial guidance for the year. We are delighted that a growing number of cell therapy developers are partnering with PCT to take advantage of our expertise and our quality, scalable, innovative, reliable and cost-efficient manufacturing platforms and services to advance their cellular therapies."

"Our leadership in regenerative and cell therapy was further solidified with the appointment of Dr. Robert Preti as Chairman of ARM. As a pioneer in cell therapy manufacturing and development, Dr. Preti remains at the forefront of the industry, influencing regulatory trends and policy making. ARM’s dedication to advancing regenerative medicine and cell therapies and to bringing its stakeholders together is unprecedented, and aligns with PCT’s vision of contributing to a world in which transformative cell-based therapeutics are accessible to all patients in need," concluded Dr. Mazzo.

Second Quarter Financial Highlights

Total revenues for the second quarter of 2016 increased 41% to $8.3 million compared with $5.9 million for the second quarter of 2015. Gross margin on revenues was 15% in the second quarter of 2016 compared with 1% in the second quarter of 2015.

Research and development (R&D) expenses for the second quarter of 2016 decreased 47% to $4.0 million compared with $7.6 million for the second quarter of 2015. The decrease was primarily related to lower costs subsequent to the discontinuation of the Intus Phase 3 clinical trial for metastatic melanoma as well as lower program expenses associated with the Company’s ischemic repair platform, compared with the prior-year period. These decreases were partially offset by an increase in expenses related to The Sanford Project: T-Rex Phase 2 Study in T1D.

Selling, general and administrative (SG&A) expenses decreased 46% to $4.7 million for the second quarter of 2016 compared with $8.7 million for the same period in 2015. The decrease is due to both lower equity-based compensation costs and operational and compensation-related cost reductions compared to the prior year period.

The operating loss for the second quarter of 2016 was $7.5 million compared with an operating loss of $25.7 million for the second quarter of 2015, reflecting higher revenues and gross margin, and lower R&D and SG&A expenses, as well as an impairment of intangible assets in the second quarter of 2015.

The Company reported a net loss for the second quarter of 2016 of $7.9 million, or $1.33 per share, compared with a net loss for the second quarter of 2015 of $17.2 million, or $3.84 per share.

First Half Financial Highlights

Total revenues for the six months ended June 30, 2016 increased 75% to $15.8 million compared with $9.0 million for the first six months of 2015. Gross margin for the first half of 2016 was 16% compared with a negative 1% for the first half of 2015.

R&D expenses for the first half of 2016 decreased to $9.9 million compared with $14.4 million for the first half of 2015. SG&A expenses decreased to $11.2 million for the first half of 2016 compared with $19.8 million for the same period in 2015. The first half of 2015 included expenses associated with executive management changes including one-time new hire compensation-related costs. The first half of 2016 included separation-related costs incurred during the first quarter of 2016, while equity-based compensation expenses were significantly lower in the first half of 2016 compared to the prior year period.

The operating loss for the first half of 2016 was $18.6 million compared with an operating loss of $43.8 million for the first half of 2015.

The net loss for the six months ended June 30, 2016 was $19.9 million, or $3.39 per share, compared with a net loss for the six months ended June 30, 2015 of $36.4 million, or $8.83 per share.

Balance Sheet and Cash Flow Highlights

As of June 30, 2016, Caladrius had cash and cash equivalents of $17.7 million. Net cash used in operating activities for the six months ended June 30, 2016 was $14.6 million, compared with $21.8 million for the six months ended June 30, 2015.

2016 Financial Guidance

The Company reaffirms its previous guidance as follows:

•
Consolidated Revenues: to exceed $30 million or a greater than 30% increase compared with 2015
•
Capital Improvements at PCT’s Allendale, NJ facility: ~$6 million, to be completed by end of first half of 2017
•
CLBS03 Phase 2 Study Costs in 2016: $6 million to $7 million
•
Consolidated Annual Operating Cash Burn: $25 million to $28 million in 2016, with lower operating cash burn in the second half of 2016 than in the first half of the year

On August 9, 2016 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the second quarter of 2016 and updated financial guidance for 2016 (Press release, Jazz Pharmaceuticals, AUG 9, 2016, View Source;p=RssLanding&cat=news&id=2194317 [SID:1234514477]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have made significant progress in 2016, as we continue to build the foundation for future growth by further diversifying and strengthening our hematology/oncology portfolio with the addition of Vyxeos, a late-stage product candidate for the treatment of acute myeloid leukemia, through the acquisition of Celator Pharmaceuticals," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "We achieved strong organic sales growth of our key products, including a significant contribution from the U.S. launch of Defitelio, received FDA approval of our manufacturing facility in Athlone, Ireland and entered into additional corporate development transactions with the potential to bring innovative treatment options to patients."

GAAP net income attributable to Jazz Pharmaceuticals plc for the second quarter of 2016 was $111.3 million, or $1.80 per diluted share, compared to $88.1 million, or $1.40 per diluted share, for the second quarter of 2015.

The company has modified the calculation of its non-GAAP income tax provision and has reflected this modification in its 2015 and 2016 non-GAAP interim period results and full-year 2016 financial guidance in connection with the Securities and Exchange Commission’s May 2016 guidance pertaining to non-GAAP financial measures. The company’s modified calculation no longer includes the cash tax benefits the company realizes during the year from net operating losses and credits and deductible share-based compensation and now includes other deferred taxes and changes in unrecognized tax benefits. This modification does not change the amount of cash taxes that the company expects to pay in 2016 or in the future, and therefore has no impact on the company’s future expected cash flows. This modification does not reflect a change in the amount of cash taxes that the company expects to pay in 2016, or in the future, or a change to the company’s expected future cash flows.

Adjusted net income attributable to Jazz Pharmaceuticals plc for the second quarter of 2016 was $162.6 million, or $2.63 per diluted share. Without giving effect to the modification described above, adjusted net income attributable to Jazz Pharmaceuticals plc for the second quarter of 2016 would have been $174.3 million, or $2.82 per diluted share. Adjusted net income attributable to Jazz Pharmaceuticals plc for the second quarter of 2015 was $144.2 million, or $2.28 per diluted share. Without giving effect to the modification described above, adjusted net income attributable to Jazz Pharmaceuticals plc for the second quarter of 2015 was previously reported as $152.2 million, or $2.41 per diluted share. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included in this press release.

Financial Highlights

Three Months Ended
June 30,

Six Months Ended
June 30,

(In thousands, except per share amounts and percentages)
2016

2015

Change

2016

2015

Change
Total revenues
$
381,161

$
333,747

14.2
%

$
717,171

$
643,050

11.5
%
GAAP net income attributable to Jazz Pharmaceuticals plc
$
111,282

$
88,114

26.3
%

$
185,403

$
158,814

16.7
%
Adjusted net income attributable to Jazz Pharmaceuticals plc1
$
162,584

$
144,151

12.8
%

$
295,461

$
259,666

13.8
%
GAAP EPS attributable to Jazz Pharmaceuticals plc
$
1.80

$
1.40

28.6
%

$
2.98

$
2.52

18.3
%
Adjusted EPS attributable to Jazz Pharmaceuticals plc1
$
2.63

$
2.28

15.4
%

$
4.75

$
4.12

15.3
%
____________________________

1.
Without giving effect to the modification of the calculation of non-GAAP income tax provision described above, adjusted net income attributable to Jazz Pharmaceuticals plc would have been $174.3 million, or $2.82 per diluted share, and was previously reported as $152.2 million, or $2.41 per diluted share, for the three months ended June 30, 2016 and 2015, respectively. Without giving effect to the modification described above, adjusted net income attributable to Jazz Pharmaceuticals plc would have been $315.3 million, or $5.07 per diluted share, and was previously reported as $277.2 million, or $4.40 per diluted share, for the six months ended June 30, 2016 and 2015, respectively.

Total Revenues

Three Months Ended
June 30,

Six Months Ended
June 30,
(In thousands)
2016

2015

2016

2015
Xyrem (sodium oxybate) oral solution
$
280,968

$
247,846

$
530,505

$
460,536

Erwinaze / Erwinase (asparaginase Erwinia chrysanthemi)
49,748

46,151

100,921

96,504

Defitelio (defibrotide sodium) / defibrotide
33,246

15,257

51,143

32,620

Prialt (ziconotide) intrathecal infusion
8,073

7,138

14,282

13,902

Psychiatry
3,867

9,372

10,869

18,465

Other
3,208

6,342

5,306

17,114

Product sales, net
379,110

332,106

713,026

639,141

Royalties and contract revenues
2,051

1,641

4,145

3,909

Total revenues
$
381,161

$
333,747

$
717,171

$
643,050

Net product sales increased 14% in the second quarter of 2016 compared to the same period in 2015 due to higher net product sales of Xyrem, Erwinaze and Defitelio.

Xyrem net product sales increased 13% in the second quarter of 2016 compared to the same period in 2015.

Erwinaze/Erwinase net product sales increased 8% in the second quarter of 2016 compared to the same period in 2015. While Erwinaze net product sales increased, the company expects to continue to experience inventory and supply challenges, which may result in temporary disruptions in the company’s ability to supply certain markets, including the U.S., from time to time. The company continues to work with distributors to prioritize delivery of drug to institutions for the treatment of patients who have been prescribed Erwinaze.

Defitelio/defibrotide net product sales increased $18.0 million in the second quarter of 2016 compared to the same period in 2015. The increase in net product sales was due to net sales of $9.5 million following the April 2016 launch of Defitelio in the U.S. and a significant increase in net product sales outside of the U.S.

Operating Expenses

Three Months Ended
June 30,

Six Months Ended
June 30,
(In thousands, except percentages)
2016

2015

2016

2015
GAAP:

Cost of product sales
$
23,980

$
21,813

$
47,419

$
50,111

Gross margin
93.7
%

93.4
%

93.3
%

92.2
%
Selling, general and administrative
$
122,618

$
107,132

$
251,383

$
219,520

% of total revenues
32.2
%

32.1
%

35.1
%

34.1
%
Research and development
$
39,091

$
27,833

$
70,343

$
55,014

% of total revenues
10.3
%

8.3
%

9.8
%

8.6
%
Acquired in-process research and development
$
—

$
—

$
8,750

$
—

Non-GAAP adjusted:

Cost of product sales
$
23,017

$
21,041

$
45,657

$
48,644

Gross margin
93.9
%

93.7
%

93.6
%

92.4
%
Selling, general and administrative
$
99,488

$
88,470

$
202,099

$
183,511

% of total revenues
26.1
%

26.5
%

28.2
%

28.5
%
Research and development
$
35,562

$
23,967

$
63,524

$
47,663

% of total revenues
9.3
%

7.2
%

8.9
%

7.4
%

Operating expenses changed over the prior year period primarily due to the following:

Selling, general and administrative (SG&A) expenses increased in the second quarter of 2016 compared to the same period in 2015, on a GAAP and on a non-GAAP adjusted basis, primarily due to higher headcount and other expenses resulting from the expansion of the company’s business.
Research and development (R&D) expenses increased in the second quarter of 2016 compared to the same period in 2015, on a GAAP and on a non-GAAP adjusted basis, primarily due to higher costs for clinical studies and outside services for the development of JZP-110 and line extensions for the company’s existing products.
Cash Flow and Balance Sheet

As of June 30, 2016, cash, cash equivalents and investments were $916.4 million, and the outstanding principal balance of the company’s long-term debt was $1.3 billion. Cash, cash equivalents and investments decreased from December 31, 2015 primarily due to repurchases under the company’s share repurchase program and a $150.0 million milestone payment triggered by the U.S. Food and Drug Administration (FDA) approval of Defitelio on March 30, 2016, partially offset by cash generated by the business. During the six months ended June 30, 2016, the company repurchased 1.3 million ordinary shares for $163.2 million, at an average cost of $126.74 per ordinary share.

Recent Developments

In June 2016, the company received FDA approval for its manufacturing facility in Athlone, Ireland. Xyrem and certain development product candidates will be manufactured in this facility.

On July 12, 2016, the company completed its acquisition of Celator Pharmaceuticals, Inc. for approximately $1.5 billion.

On July 12, 2016, the company amended its existing credit agreement by increasing the revolving credit facility to $1.25 billion from $750 million and extending the maturity date of the term loan facility and revolving credit facility to July 2021 from June 2020. The company used borrowings of $1.0 billion under the company’s revolving credit facility, together with cash on hand, to fund the Celator acquisition, resulting in an increase of the outstanding principal balance of long-term debt to approximately $2.3 billion.

On August 2, 2016, the U.S. Centers for Medicare and Medicaid Services approved a New Technology Add-on Payment (NTAP) for Defitelio after determining that Defitelio met the NTAP criteria for newness, substantial clinical improvement relative to existing therapies and specific cost thresholds. Beginning October 1, 2016, NTAP will provide incremental reimbursement to the standard diagnosis-related group based reimbursement for Defitelio, which should support Medicare beneficiaries’ access to Defitelio when treated in certain inpatient hospital settings.

2016 Financial Guidance*

Jazz Pharmaceuticals is updating its full year 2016 financial guidance primarily due to the acquisition of Celator Pharmaceuticals and modification of the calculation of non-GAAP income tax provision, as follows (in millions, except per share amounts and percentage):

Revenues
$1,485-$1,530
Total net product sales
$1,477-$1,522
-Xyrem net sales
$1,095-$1,130
-Erwinaze/Erwinase net sales
$190-$215
-Defitelio/defibrotide net sales
$105-$125
GAAP gross margin %
93%
Non-GAAP adjusted gross margin %1,4
93%
GAAP SG&A expenses
$499-$529
Non-GAAP adjusted SG&A expenses2,4
$400-$415
GAAP R&D expenses
$149-$161
Non-GAAP adjusted R&D expenses3,4
$135-$145
GAAP net income per diluted share
$5.66-$6.56
Non-GAAP adjusted net income per diluted share4
$9.90-$10.30
____________________________

*
Updated August 9, 2016. The company’s 2016 financial guidance remains subject to final acquisition accounting adjustments for the acquisition of Celator Pharmaceuticals.

1.
Excludes $5 million of share-based compensation expense from estimated GAAP gross margin.
2.
Excludes $78-$86 million of share-based compensation expense, $15-$22 million of transaction and integration related costs and $6 million of expenses related to certain legal proceedings and restructuring from estimated GAAP SG&A expenses.
3.
Excludes $14-$16 million of share-based compensation expense from estimated GAAP R&D expenses.
4.
See "Non-GAAP Financial Measures" below. Reconciliations of non-GAAP adjusted guidance measures are included above and in the table titled "Reconciliation of GAAP to Non-GAAP Adjusted 2016 Net Income Guidance" provided on the last page of this press release.

On August 9, 2016 Intrexon Corporation (NYSE: XON), a leader in the engineering and industrialization of biology to improve the quality of life and health of the planet, reported its second quarter and first half financial results for 2016 (Press release, Intrexon, AUG 9, 2016, View Source [SID:1234514476]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Business Highlights and Recent Developments:

The U.S. Food and Drug Administration (FDA) published final finding of no significant impact and final environmental assessment on Oxitec’s OX513A self-limiting mosquito concluding that a field trial of the Friendly Aedes in Key Haven, Florida, will not result in a significant impact on the environment;
Expanded Oxitec’s ‘Friendly Aedes aegypti Project’ in Piracicaba, Brazil to an area in the city’s center covering 60,000 residents. Releases of Friendly Aedes, the mosquito that fights the primary vector of dengue, Zika and chikungunya, began in July;
Oxitec reported results from Piracicaba’s Epidemiologic Surveillance service which showed a 91% reduction of dengue fever cases registered in the 2015/2016 dengue-year as compared to the 2014/2015 period in the CECAP/Eldorado district, an area of 5,000 residents and the initial site of the ‘Friendly Aedes aegypti Project’;
Announced Grand Cayman will use Oxitec’s Friendly Aedes to suppress wild Aedes aegypti in an effort to help eliminate diseases transmitted by this mosquito. Releases of Friendly Aedes began in July;
Announced the formation of Intrexon Crop Protection (ICP), a wholly-owned subsidiary dedicated to bio-based control of agricultural pests and diseases through the utilization of Oxitec’s diverse self-limiting gene platform for species-specific insect control, as well as the ActoBiotics system for the expression of targeted biologicals for pest and disease management programs;
Introduced Florian technology, an "on-off" regulation switch system which exhibits the capability to regulate the timing of flowering, as well as selectively activate specific plant genes, through topical application of an activator. This technology demonstrates potential for enabling a variety of commercial applications in agriculture, and the Company will focus its initial efforts on near-to-market opportunities in turf, floral, and forage industries;
Announced amendments to Exclusive Channel Collaborations (ECCs) with ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) in the fields of oncology and graft-versus-host-disease to improve alignment. Operating profit rates payable to Intrexon from ZIOPHARM on products developed under these ECCs decrease from 50% to 20%, excluding the companies’ existing collaboration with Merck Serono, the biopharmaceutical division of Merck KGaA. Economics from any future sublicensing arrangements with third party collaborators will be split evenly. Intrexon received $120 million in ZIOPHARM preferred stock along with a monthly dividend of 1% payable in additional preferred shares;
Collaborator ZIOPHARM announced plans for a Phase I clinical trial utilizing autologous T cells transduced with lentivirus to express a CD33-specific chimeric antigen receptor (CAR) in patients with relapsed or refractory acute myeloid leukemia. This will be second trial initiated at The University of Texas MD Anderson Cancer Center under the research and development agreement among ZIOPHARM, Intrexon, and MD Anderson to expeditiously move promising treatments from bench to clinic;
Entered into an ECC with AD Skincare, Inc., backed by the Harvest Intrexon Enterprise Fund, sponsored by Harvest Capital Strategies, LLC, which will focus on developing an advanced delivery system for anti-aging active ingredients to be used in cosmetic formulations that are designed to reduce the appearance of certain signs of aging on human facial skin;
Collaborator Fibrocell Science, Inc. (NASDAQ: FCSC) initiated adult patient recruitment in its Phase I/II clinical trial of FCX-007 in June and during July reported the first two adult subjects had been enrolled. Fibrocell expects to commence dosing this year;
Two Intrexon collaborators’ gene therapy programs received Orphan Drug designation from the FDA: Fibrocell’s FCX-013 for the treatment of linear scleroderma and Agilis Biotherapeutics’ AGIL-FA for the treatment of Friedreich’s ataxia;
Exemplar Genetics announced the FDA exercised enforcement discretion in regard to its ExeGen low-density lipoprotein receptor miniswine, clearing this animal that enables superior translational research and better predictive efficacy for commercial use as a research model;
Intrexon’s subsidiary AquaBounty Technologies, Inc. (AIM: ABTU; OTC: AQBT) received approval from Health Canada for commercial sale of AquAdvantage Salmon (AAS) in Canada;
Appointed Geno Germano, a pharmaceutical executive with over 30 years of experience, to the new role of President, helping lead Intrexon’s management team and commercialization efforts;
Appointed Andrew J. Last, Ph.D., a seasoned executive with 30 years of experience spanning life sciences, including biotechnology, genomics, clinical diagnostics, pharmaceuticals and agrochemicals, as Chief Operating Officer, to oversee Intrexon’s multiple technology divisions and operating subsidiaries; and
Appointed distinguished life sciences executive Fred Hassan to Intrexon’s Board of Directors.
Second Quarter Financial Highlights:

Total revenues of $52.5 million, an increase of 17% over the second quarter of 2015;
Net loss of $49.1 million attributable to Intrexon, or $(0.42) per basic share, including non-cash charges of $44.0 million;
Adjusted EBITDA of $110.7 million, or $0.94 per basic share;
Cash consideration received for reimbursement of research and development services covered 59% of cash operating expenses (exclusive of operating expenses of consolidated subsidiaries);
Total consideration received for technology access fees, reimbursement of research and development services and products and services revenues covered 279% of consolidated cash operating expenses; and
Cash, cash equivalents, and short-term and long-term investments totaled $321.2 million, the value of investment in preferred stock totaled $120.0 million, and the value of marketable equity securities totaled $39.0 million at June 30, 2016.
First Half Financial Highlights:

Total revenues of $95.9 million, an increase of 22% over the first half of 2015;
Net loss of $113.5 million attributable to Intrexon, or $(0.97) per basic share, including non-cash charges of $94.6 million;
Adjusted EBITDA of $112.5 million, or $0.96 per basic share;
Cash consideration received for reimbursement of research and development services covered 57% of cash operating expenses (exclusive of operating expenses of consolidated subsidiaries); and
Total consideration received for technology access fees, reimbursement of research and development services and products and services revenues covered 184% of consolidated cash operating expenses.
"We began the year with great anticipation that 2016 will be a period in which we should demonstrate significant progress on several dimensions," commented Randal J. Kirk, Chairman and Chief Executive Officer of Intrexon, "and so far are tracking very well against our objectives. While continuing our trajectory of growing financial performance and capital efficiency, we have advanced many of our programs, achieving key scientific, developmental and regulatory milestones. In addition, our production and marketing plans around three mature yet game-changing assets – the Friendly Aedes mosquito, the Arctic apple and the AquAdvantage salmon – are being managed aggressively, and we look forward to the world enjoying the benefits of each of these unique, sustainable and environmentally responsible solutions to major problems."

Mr. Kirk concluded, "Considering the poignant moment in history that we occupy, one in which there is increasing recognition of the need for the engineering of biology to be responsibly practiced in order to solve an enormous number of world problems in areas such as healthcare, food, energy and the environment, our greatest need in order for Intrexon to play a leading role on this industrial and social vector, is the recruitment and development of great talent at every level of our organization – on our board, within our executive management team and in our labs that today span North America and Europe. In this regard, I am honored every day to work in partnership with our President, Geno Germano, the rest of our executive team and with so many brilliant and dedicated scientists and professionals throughout our organization. I believe that the world should expect great things from such a team, and I believe that they will deliver on these expectations. "

Second Quarter 2016 Financial Results Compared to Prior Year Period
Total revenues were $52.5 million for the quarter ended June 30, 2016 compared to $44.9 million for the quarter ended June 30, 2015, an increase of $7.6 million, or 17%. Collaboration and licensing revenues increased $10.3 million over the quarter ended June 30, 2015 due to (i) the recognition of deferred revenue for upfront payments received from the Company’s license and collaboration agreement with the biopharmaceutical business of Merck KGaA, which became effective in May 2015, and from other collaborations signed by Intrexon between July 1, 2015 and June 30, 2016; and (ii) increased research and development services for these collaborations and for the progression of programs or the addition of new programs with previously existing collaborators. Product revenues were $10.9 million for the quarter ended June 30, 2016 compared to $14.3 million for the quarter ended June 30, 2015, a decrease of $3.4 million, or 24%. The decrease in product revenues and gross margin thereon primarily relates to a decrease in the quantities of pregnant cows, livestock previously used in production and live calves sold due to lower customer demand for these products. The decreases were partially offset by an increase in the quantity of weaned calves sold due to higher customer demand. Service revenues were $13.9 million for the quarter ended June 30, 2016 compared to $13.3 million for the quarter ended June 30, 2015, an increase of $0.6 million, or 5%. The increase relates to an increase in the number of in vitro fertilization cycles performed due to higher customer demand.

Total operating expenses were $75.7 million for the quarter ended June 30, 2016 compared to $62.3 million for the quarter ended June 30, 2015, an increase of $13.4 million, or 22%. Research and development expenses increased $8.0 million, or 39%, due primarily to increases in (i) salaries, benefits and other personnel costs for research and development employees, (ii) lab supplies and consulting expenses, and (iii) depreciation and amortization. Salaries, benefits and other personnel costs increased $2.3 million due to (i) an increase in research and development headcount to support new and expanded collaborations and (ii) costs for research and development employees assumed in the Company’s acquisition of Oxitec Limited, or Oxitec, in September 2015. Lab supplies and consulting expenses increased $3.4 million as a result of (i) the progression into the preclinical phase with certain of Intrexon’s collaborators; (ii) the increased level of research and development services provided to the Company’s collaborators; and (iii) costs incurred as a result of the Company’s September 2015 acquisition of Oxitec. Depreciation and amortization increased $1.9 million primarily as a result of (i) the inclusion of a full quarter of depreciation and amortization on property and equipment and intangible assets acquired in the Company’s 2015 acquisitions, and (ii) amortization related to AquaBounty’s intangible assets upon regulatory approval in November 2015. Selling, general and administrative (SG&A) expenses increased $6.6 million, or 28%, over the second quarter of 2015. Legal and professional expenses increased $5.8 million due to (i) consulting expenses payable in shares of Intrexon’s common stock pursuant to the Company’s services agreement with Third Security, LLC, or Third Security, which the Company entered into in November 2015; (ii) expenses incurred to support domestic and international government affairs for regulatory and other approvals necessary to commercialize the Company’s products and services; (iii) increased legal fees incurred to defend ongoing litigation; and (iv) incremental costs incurred to support the ongoing operations of the Company’s 2015 acquisitions and other business development activities. These increases were partially offset by a decrease of $2.2 million for salaries, benefits and other personnel costs. Salaries, benefits and other personnel costs for SG&A employees decreased primarily due to a decrease in stock compensation and other compensation expenses resulting primarily from the departure of certain officers of the Company. These decreases were partially offset by increased headcount, including a new executive officer to support the Company’s expanding operations as well as the acquisition of Oxitec in September 2015.

First Half 2016 Financial Results Compared to Prior Year Period
Total revenues were $95.9 million for the six months ended June 30, 2016 compared to $78.7 million for the six months ended June 30, 2015, an increase of $17.2 million, or 22%. Collaboration and licensing revenues increased $19.6 million over the six months ended June 30, 2015 due to (i) the recognition of deferred revenue for upfront payments received from the Company’s license and collaboration agreement with the biopharmaceutical business of Merck KGaA, which became effective in May 2015, and from other collaborations signed by Intrexon between July 1, 2015 and June 30, 2016; and (ii) increased research and development services for these collaborations and for the progression of programs or the addition of new programs with previously existing collaborators. Product revenues were $19.4 million for the six months ended June 30, 2016 compared to $23.2 million for the six months ended June 30, 2015, a decrease of $3.8 million, or 16%. The decrease in product revenues and gross margin thereon primarily relates to a decrease in the quantities of pregnant cows, livestock previously used in production and live calves sold due to lower customer demand for these products. The decreases were partially offset by an increase in the quantity of weaned calves sold due to higher customer demand. Service revenues were $24.6 million for the six months ended June 30, 2016 compared to $23.2 million for the six months ended June 30, 2015, an increase of $1.4 million, or 6%. The increase relates to an increase in the number of in vitro fertilization cycles performed due to higher customer demand.

Total operating expenses were $159.7 million for the six months ended June 30, 2016 compared to $183.3 million for the six months ended June 30, 2015, a decrease of $23.6 million, or 13%. Research and development expenses declined $45.5 million, or 46%, due primarily to the inclusion in 2015 of a $59.6 million payment In common stock for an exclusive license to certain technologies owned by the University of Texas MD Anderson Cancer Center. This decrease was partially offset by increases in (i) salaries, benefits and other personnel costs for research and development employees, (ii) lab supplies and consulting expenses, and (iii) depreciation and amortization. Salaries, benefits and other personnel costs increased $4.6 million due to (i) an increase in research and development headcount to support new and expanded collaborations and (ii) costs for research and development employees assumed in the Company’s acquisition of Oxitec in September 2015. Lab supplies and consulting expenses increased $6.2 million as a result of (i) the progression into the preclinical phase with certain of Intrexon’s collaborators; (ii) the increased level of research and development services provided to the Company’s collaborators; and (iii) costs incurred as a result of the Company’s September 2015 acquisition of Oxitec. Depreciation and amortization increased $3.8 million primarily as a result of (i) the inclusion of a full period of depreciation and amortization on property and equipment and intangible assets acquired in the Company’s 2015 acquisitions and (ii) amortization related to AquaBounty’s intangible assets upon regulatory approval in November 2015. SG&A expenses increased $21.8 million, or 43%, over the six months of 2015. Salaries, benefits and other personnel costs for SG&A employees increased $3.8 million due to (i) increased headcount, including a new executive officer, to support the Company’s expanding operations; (ii) a full period of stock compensation expense for a company-wide option grant to employees in March 2015; and (iii) salaries, benefits and other personnel costs for employees assumed in the Company’s acquisition of Oxitec in September 2015. These increases were partially offset by (i) a decrease in stock compensation and other compensation expenses resulting primarily from the departure of certain officers of the Company. Legal and professional expenses increased $9.5 million primarily due to (i) consulting expenses payable in shares of Intrexon’s common stock pursuant to the Company’s services agreement with Third Security which the Company entered into in November 2015; (ii) expenses incurred to support domestic and international government affairs for regulatory and other approvals necessary to commercialize the Company’s products and services; (iii) increased legal fees incurred to defend ongoing litigation; and (iv) incremental costs incurred to support the ongoing operations of the Company’s 2015 acquisitions and other business development activities. In 2016, the Company also recorded $4.2 million in litigation settlement expenses arising from the entrance of a court order in Trans Ova Genetics, L.C.’s trial with XY, LLC.

Total other income (expense), net, was $(43.8 million) for the six months ended June 30, 2016 compared to $94.7 million for the six months ended June 30, 2015, a decrease of $138.5 million, or 146%. This decrease was attributable to the $81.4 million realized gain recognized upon the special stock dividend of all of Intrexon’s shares of ZIOPHARM to the Company’s shareholders in June 2015 and the decrease in fair value of the Company’s equity securities portfolio.

On August 9, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported its second quarter 2016 financial results (Press release, Infinity Pharmaceuticals, AUG 9, 2016, View Source;p=RssLanding&cat=news&id=2194286 [SID:1234514475]). Additionally, the company provided an update on its two development programs, duvelisib, an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, and IPI-549, an immuno-oncology development candidate that selectively inhibits PI3K-gamma. Infinity is continuing to explore a broad range of strategic options for duvelisib, including a potential sale of the program. In parallel, the company continues to advance key value drivers for duvelisib. Infinity is also proceeding with its planned development of IPI-549 in multiple solid tumors and evaluating the best path forward for this development candidate.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Data reported to date have demonstrated that duvelisib could play an important role in the future treatment of patients with hematologic malignancies, particularly for relapsing and/or refractory patients. We are now exploring strategic options for the program that could enable duvelisib to continue to advance toward potential regulatory filings and commercialization," stated Adelene Perkins, president and chief executive officer. "We are also developing IPI-549 and determining the best clinical path forward for this promising immuno-oncology program. The Phase 1 study, which includes evaluation of IPI-549 as a monotherapy and planned evaluation in combination with a checkpoint inhibitor, is progressing well, and new preclinical and clinical data on IPI-549 will be presented at an immuno-oncology conference next month."

Today Infinity also announced that DUO, a Phase 3, randomized monotherapy study of duvelisib compared to ofatumumab in 319 patients with relapsed or refractory chronic lymphocytic leukemia (CLL), will proceed to its final analysis. The primary endpoint of the study is progression-free survival, and the event that will trigger the final analysis is expected to occur in the fourth quarter of 2016. If the DUO data are positive, Infinity continues to believe that the study could provide the basis for regulatory approval in CLL. Earlier this year, Infinity reported that DYNAMO, a registration-focused Phase 2 monotherapy study evaluating the efficacy and safety of duvelisib in patients with refractory indolent non-Hodgkin lymphoma (iNHL), met its primary endpoint of overall response rate and that the company intends to seek feedback on these data from the U.S. Food and Drug Administration (FDA). Infinity is continuing to advance activities to enable potential regulatory filings for duvelisib. While exploring the potential sale of the program, Infinity is suspending its prior guidance on the nature and timing of additional duvelisib program updates, including guidance on data from duvelisib registration-focused trials and timing of potential regulatory filings.

Recent developments include the following:
Duvelisib

Topline data from DYNAMO reported: In June, Infinity announced that DYNAMO, a registration-focused Phase 2 monotherapy study evaluating the efficacy and safety of duvelisib in 129 patients with refractory iNHL, met its primary endpoint of overall response rate. In the study, duvelisib demonstrated an overall response rate (ORR) of 46 percent. The majority of reported side effects were reversible and clinically manageable. Infinity plans to seek feedback from the FDA on these data.

Data from CONTEMPO presented at EHA (Free EHA Whitepaper): In June, researchers presented preliminary data from CONTEMPO, a Phase 1b/2 clinical study evaluating duvelisib in combination with rituximab or obinutuzumab in treatment-naïve patients with follicular lymphoma, at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper). Duvelisib in combination with Gazyva (obinutuzumab) demonstrated an overall response rate of 100 percent, including a 33 percent complete response rate among nine patients evaluable for response, and duvelisib in combination with Rituxan (rituximab) demonstrated an overall response rate of 80 percent, including a 30 percent complete response among 10 patients evaluable for response. The preliminary safety profile of duvelisib in combination with either obinutuzumab or rituximab in treatment-naïve patients with follicular lymphoma was in line with the safety profile of duvelisib as monotherapy. The CONTEMPO study is ongoing having enrolled 55 patients and is now closed to additional patient enrollment.

Further duvelisib regulatory and clinical update: Infinity continues to advance preparations for potential regulatory submissions to support approval of duvelisib based on the DYNAMO and, if the data are positive, DUO studies. In addition to the DYNAMO, DUO and CONTEMPO studies described earlier, the SYNCHRONY and FRESCO studies are ongoing to support the potential approval and launch of duvelisib in CLL and follicular lymphoma. SYNCHRONY is a Phase 1b combination study of duvelisib plus obinutuzumab in CLL or small lymphocytic lymphoma patients who were previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor. FRESCO is a randomized study of duvelisib in combination with rituximab compared to R-CHOP in patients with relapsed/refractory follicular lymphoma designed to evaluate the potential of duvelisib as an alternative treatment option to chemotherapy. In June, Infinity announced that it was closing BRAVURA, a Phase 3 study of duvelisib in patients with relapsed iNHL, to align resources to its strategic objectives regarding duvelisib.
IPI-549

Phase 1 study of IPI-549 ongoing: A Phase 1 study of IPI-549 is ongoing to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with an anti-PD-1 antibody, a checkpoint inhibitor, in approximately 150 patients with advanced solid tumors, including non-small cell lung cancer and melanoma. IPI-549 is the only investigational PI3K-gamma inhibitor in clinical development. Infinity expects to initiate cohorts studying IPI-549 in combination with an anti-PD-1 antibody this Fall.

New data on IPI-549 to be presented at upcoming scientific meeting: Infinity announced today that preclinical and clinical data on IPI-549 will be presented at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival taking place September 25-28, 2016, in New York City.

Manuscript describing discovery of IPI-549 accepted for publication: Infinity reported that a manuscript describing the company’s medicinal chemistry research efforts that led to the discovery of IPI-549 has been accepted for publication in ACS Medicinal Chemistry Letters. The paper, "Discovery of a selective phosphoinositide-3-kinase (PI3K)-gamma inhibitor (IPI-549) as an immuno-oncology clinical candidate," describes the evaluation of a focused group of PI3K-gamma inhibitors resulting in the selection of IPI-549 as a development candidate based on its potency, selectivity, favorable in vitro safety and pharmacokinetic profile and ability to inhibit PI3K-gamma in vivo.1 A preliminary copy of the manuscript is currently available on the ACS Publications website.
Corporate

June restructuring of workforce nearly completed: In June, Infinity undertook two strategic restructurings in order to preserve financial resources. In summary, the company reduced its employee headcount by approximately 66 percent compared to its employee headcount as of December 31, 2015. The June restructurings impacted all functions across the organization and have been nearly completed.
The restructuring also included a non-cash impairment loss of $2.3 million related to fixed assets that were written down to fair value during the three months ended June 30, 2016.

Infinity is also evaluating its current facility leases. If Infinity pursues and successfully restructures these facility leases in 2016, it could potentially incur additional charges during the second half of 2016 upon exit of the space.

Second Quarter 2016 Financial Results

At June 30, 2016, Infinity had total cash, cash equivalents and available-for-sale securities of $146.4 million, compared to $193.0 million at March 31, 2016.

Revenue during the second quarter of 2016 was $9.5 million for research and development (R&D) services associated with the collaboration with AbbVie for duvelisib in oncology up through AbbVie’s opt-out, compared to $4.9 million for R&D services for the second quarter of 2015.

R&D expense for the second quarter of 2016 was $52.9 million, compared to $34.1 million for the second quarter of 2015. The increase in R&D expense was primarily due to restructuring activities as well as higher clinical development expenses for duvelisib. In the second quarter of 2016, the company recognized $11.9 million of restructuring charges within R&D expense.

General and administrative (G&A) expense was $15.7 million for the second quarter of 2016, compared to $9.4 million for the same period in 2015. The increase in G&A expense was primarily related to restructuring activities. In the second quarter of 2016, the company recognized $4.7 million of restructuring charges within G&A expense.

Infinity recorded a non-recurring gain on AbbVie opt-out of the duvelisib collaboration of $112.2 million for the second quarter of 2016. The AbbVie opt-out is irrevocable, and Infinity has no obligation to continue to provide AbbVie any services. There were no gains for the second quarter of 2015.

Net income for the second quarter of 2016 was $53.0 million, or a basic and diluted earnings per common share of $1.05, compared to a net loss of $38.4 million, or a basic and diluted loss per common share of $0.78, for the same period in 2015.
Cash and Investments Outlook
Following the AbbVie opt-out and Infinity’s restructuring activities, Infinity today provided an update on its anticipated year-end 2016 cash and investments balance. In the absence of additional funding or proceeds from business development activities, including the potential sale of duvelisib:

Infinity expects to end 2016 with a year-end cash and investments balance ranging from $45 million to $55 million, compared to prior expectations of $45 million to $65 million.

Infinity expects that its existing cash, cash equivalents and available-for-sale securities at June 30, 2016, will be adequate to satisfy the company’s capital needs into the third quarter of 2017 based on its current operational plans, compared to previous guidance of cash runway through the first quarter of 2017. The extension of the company’s cash runway is the result of its June restructuring activities and expectations that it does not expect to incur duvelisib expenses beyond the fourth quarter of 2016, consistent with Infinity’s current focus on selling the program.

On August 9, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) reported financial results for the second quarter ended June 30, 2016, and provided an update on the Company’s recent activities (Press release, Ziopharm, AUG 9, 2016, View Source [SID:1234514473]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"ZIOPHARM had a very productive first half, with the achievement of pipeline and corporate milestones across the breath of our portfolio and the advancement of our goal to position the company at the forefront of those harnessing the immune system to target cancer," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. "Central to this effort, we were pleased to have amended the terms of our collaboration with Intrexon to facilitate the commercialization of our immunotherapy assets. The benefit of this new structure is expected to be first realized with our gene therapy Ad-RTS-hIL-12 + veledimex program, which remains on track to move into a registrational trial in advanced glioblastoma in 2017."

Dr. Cooper added: "As we progress through the remainder of 2016, we will continue to work with our collaborators, including Intrexon Corporation and the MD Anderson Cancer Center, to advance new therapies into the clinic. We look forward in 2016 to seeing six clinical trials exploring immuno-oncology approaches and combinations, in addition to preclinical projects advancing towards the clinic. As these programs mature, we expect to see proof-of-concept clinical data that will drive value for all of our stakeholders."

Corporate and Program Updates

Corporate

Amended Exclusive Channel Collaborations with Intrexon to Improve Alignment as Programs Advance through Development. In June, ZIOPHARM and Intrexon Corporation (NYSE:XON) announced amendments to their Exclusive Channel Collaborations (ECCs) in the fields of oncology and graft-versus-host-disease (GvHD) to improve alignment between both companies as ZIOPHARM broadens its pipeline and advances multiple therapeutic programs in the clinic.

Under the terms of the amendments:

Operating profit rates payable to Intrexon from ZIOPHARM on products developed under its two existing collaborations will be reduced from 50% to 20%. This reduction will not apply to royalties or other payments made with respect to the companies’ existing collaboration with Merck Serono, the biopharmaceutical business of Merck KGaA;

Economics from any future sublicensing arrangements with potential third party collaborators will remain evenly split.
In consideration of the amendments, ZIOPHARM has issued shares of a new class of preferred stock that carries an initial stated value of $120 million and a monthly dividend of 1%, payable in additional preferred shares. Only upon the first approval of a product in the United States or upon certain fundamental transactions, such as a change of control of ZIOPHARM, the preferred shares issued to Intrexon will be converted into ZIOPHARM common stock equal to the aggregate stated value divided by the volume weighted average closing price of ZIOPHARM’s common stock over the 20 trading days ending on the date that the product approval or such transaction is announced.

Gene Therapies

Ad-RTS-hIL-12 + veledimex is a gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating an anti-cancer immune response, using the RheoSwitch Therapeutic System (RTS) gene switch. ZIOPHARM is currently enrolling patients in two studies of Ad-RTS-hIL-12 + veledimex: a multi-center Phase 1 study in patients with recurrent or progressive glioblastoma multiforme (GBM), an aggressive form of brain cancer, and a Phase 1b/2 study for the treatment of patients with locally advanced or metastatic breast cancer following standard chemotherapy.

Presented Clinical Data Highlighting Favorable Interim Survival Results in Phase 1 Study of Ad-RTS-hIL-12 + Veledimex in Brain Cancer. ZIOPHARM presented data from its Phase 1, multi-center dose-escalation study of patients with recurrent high-grade gliomas at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held June 3-7, 2016 in Chicago and updated at an American Society of Hematology (ASH) (Free ASH Whitepaper) Workshop on Genome Editing in Washington D.C. on July 14, 2016. These data demonstrate promising early activity in this medically fragile patient population, with a median overall survival that has not been reached with 11 of 14 patients alive and in follow up, and a median follow up of 8 months with 6 patients out of 7 patients alive in the study’s first dose cohort (20mg veledimex). The study also showed that IL-12 in the bloodstream was found to be proportional to the amount of veledimex administered, demonstrating that this orally-delivered activator crossed the blood brain barrier to activate the IL-12 gene programming deposited in the tumor and turned on the RheoSwitch technology in a dose-dependent manner. In June, ZIOPHARM announced the successful completion of enrollment in the first and second dosing cohorts (40mg veledimex) of the study, as well as the initiation of enrollment in a third cohort (30mg veledimex).

Preclinical Studies Combining Ad-RTS-IL-12 + Veledimex and Immune Checkpoint Inhibitors in Brain Tumor Models Presented at ASGCT (Free ASGCT Whitepaper), Combination Study Expected to Initiate in 2016. In an oral presentation, ZIOPHARM presented data from preclinical studies of Ad-RTS-IL-12 + veledimex combined with immune checkpoint inhibitors (iCPI) in glioblastoma (GBM) mouse models at the 2016 Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper), which took place May 4-7, 2016 in Washington, D.C. Results demonstrated that survival of mice treated with Ad-RTS-IL-12 + veledimex and anti-PD-1 therapy was superior to either treatment alone, with a combination showing 100% survival. Because Ad-RTS-IL-12 and anti-PD-1 are clinically available, these data provide impetus for evaluating this combination immunotherapy in humans. ZIOPHARM plans to initiate a combination study in 2016.
Adoptive Cell Therapies

ZIOPHARM is developing various immuno-oncology programs, including chimeric antigen receptor T-cell (CAR-T), T-cell receptor (TCR), and natural killer (NK) adoptive cell-based therapies. These programs are being advanced in collaboration with Intrexon, MD Anderson Cancer Center, and Merck Serono (CAR-T only).

Announced Plans for Phase I Clinical Trial with CD33 CAR-T Cell Therapy. In July, ZIOPHARM announced plans for a Phase I adoptive cellular therapy clinical trial utilizing autologous T cells transduced with lentivirus to express a CD33-specific chimeric antigen receptor (CAR) in patients with relapsed or refractory acute myeloid leukemia (AML). The trial is based on preclinical studies, including in vitro data demonstrating that lentiviral-transduced CAR-T cells targeting CD33 exhibit specific killing activity for CD33+ AML cells and a proof-of-concept study utilizing an in vivo mouse model for AML, which showed that these CAR-T cells were able to eliminate disease and significantly enhance survival as compared to control groups. These positive preclinical results indicate biological activity and are suggestive of potential therapeutic effect for the treatment of AML.

Announced Publication of First-In-Human Trials using Non-Viral Sleeping Beauty System to Express CD19-Specific CAR in T cells in Journal of Clinical Investigation. In August, ZIOPHARM announced the publication of data highlighting the benefits of using the non-viral Sleeping Beauty (SB) system to genetically modify T cells to express a chimeric antigen receptor (CAR) for use against leukemias and lymphomas. The article, titled "Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells," was published in the Journal of Clinical Investigation (doi:10.1172/JCI86721), and is available online here.
The paper describes results for 26 patients with multiply relapsed B-lineage acute lymphoblastic leukemia (ALL, n=17) or B-cell non-Hodgkin lymphoma, (NHL, n=9) who were enrolled in two investigator-initiated clinical trials at the University of Texas MD Anderson Cancer Center infused with SB-modified T cells after autologous (n=7) or allogeneic (n=19) hematopoietic stem-cell transplantation (HSCT). Although the primary objective of these trials was not to establish efficacy, the recipients’ outcomes are encouraging, with apparent doubling of survivals compared to historical controls which is attributed to the persistence of the infused T cells. Additionally, by infusing a CD19-specific CAR T cells to target minimal residual disease after autologous and allogeneic HSCT, the approach may improve tolerability by avoiding cytokine storm.

Milestones

ZIOPHARM achieved and expects the following milestones to occur in 2016:

Intra-tumoral IL-12 RheoSwitch programs:
Clinical update presented from the Company’s Phase 1 study of GBM at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)
Update on Phase 1/2 study in Breast Cancer with standard of care presented at ASCO (Free ASCO Whitepaper)
Pre-clinical data presented at the American Society of Cell and Gene Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting for combining with checkpoint inhibitor therapy (anti PD-1)
Initiate combination study of Ad-RTS-hIL-12 with anti PD-1
CAR+ T programs:
Continuation of second generation CD19 CAR+ T clinical study
Initiate a CAR+ T clinical study for CD33
Preclinical data presented at ASGCT (Free ASGCT Whitepaper) for shortening the time of ex vivo manufacture of SB-modified T cells
Initiate CAR+ T-cell preclinical studies for other hematological malignancies and solid tumors
TCR-T programs
Initiate TCR-modified T-cell preclinical studies
NK cell programs
Initiate a Phase 1 study of off-the-shelf NK cells for AML
GvHD programs
Initiate preclinical studies
Pediatric programs
Pre-clinical data to be presented in the fall with intra-tumoral IL-12 under RheoSwitch control for brain tumor
The Company is also evaluating additional potential preclinical candidates and continuing discovery efforts aimed at identifying other potential product candidates under its Exclusive Channel Agreement with Intrexon. In addition, the Company may seek to enhance its pipeline in immuno-oncology through focused strategic transactions, which may include acquisitions, partnerships and in-licensing activities.