On August 8, 2017 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported its financial results for the second quarter ended June 30, 2017 (Press release, Calithera Biosciences, AUG 8, 2017, View Source [SID1234535256]). As of June 30, 2017, cash, cash equivalents and investments totaled $208.2 million.

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"Recent highlights included the presentation of clinical trial results of CB-1158, a first-in-class small molecule arginase inhibitor, in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), and the advancement of CB-839 into Phase 2 clinical trials in renal cell carcinoma and triple negative breast cancer," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "Looking forward to the second half of 2017, we plan to present clinical updates on CB-839, including the initial results of CB-839 dosed in combination with Bristol Myers Squibb’s Opdivo (nivolumab) in the fourth quarter."

Second Quarter 2017 and Recent Highlights

CB-839 Randomized Phase 2 Combination Trial in Renal Cell Carcinoma Initiated. In August 2017, Calithera announced the initiation of a randomized, double blind, placebo controlled trial to evaluate the safety and efficacy of CB-839 in combination with everolimus versus placebo in approximately 250 patients with metastatic, clear cell renal cell carcinoma who have been treated with at least two lines of prior systemic therapy including a VEGFR-targeting tyrosine kinase inhibitor and at least one of either CABOMETYX (cabozantinib) or an active PD-1/PD-L1 inhibitor. CB-839 has been granted Fast Track designation for this indication.

CB-839 Triple Negative Breast Cancer Phase 2 Trial Initiated. In July 2017, Calithera initiated a Phase 2 trial of CB-839 with paclitaxel in triple negative breast cancer patients. Four single arm, open label, cohorts of African American and non-African American patients will be treated in both the early stage setting, where patients have no prior treatment for metastatic disease, as well as the late stage setting, after at least two prior therapies for metastatic disease including prior taxane therapy. The primary endpoint of this trial is objective response rate. Additional data from the triple negative breast cancer development program are expected in the fourth quarter of 2017.

Collaboration with Bristol-Myers Squibb expanded. In May 2017, Calithera’s existing collaboration evaluating Opdivo (nivolumab) in combination with CB-839 was expanded to include additional renal cell carcinoma cohorts as well as non-small cell lung cancer and melanoma. Initial results of CB-839 dosed in combination with Bristol Myers Squibb’s Opdivo are expected in the fourth quarter of 2017.

CB-1158 (INCB01158) Phase I Solid Tumor Data Presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. In June 2017, data was presented from the first 17 patients with advanced solid tumors dosed with CB-1158 as a single agent. Plasma levels of arginase were inhibited > 90% in all patients, and in 10 of 11 patients plasma arginine increased 1.5-fold or more.

CB-1158 was generally well tolerated with no drug-related serious adverse events. The trial is continuing to enroll patients in the dose escalation phase of the study, and expansion cohorts in pre-defined tumor types, to be followed by combination studies with an anti-PD-1 antibody.

Selected Second Quarter 2017 Financial Results Cash, cash equivalents and investments totaled $208.2 million at June 30, 2017, compared with $207.1 million at March 31, 2017. During the second quarter of 2017, Calithera received payment of a $12.0 million milestone under its global collaboration and license agreement with Incyte.

Revenue was $7.3 million for the three months ended June 30, 2017 and represents the portion of deferred revenue recognized in the second quarter from the Company’s collaboration and license agreement with Incyte.

Research and development expenses were $10.1 million for the three months ended June 30, 2017, compared with $7.8 million for the same period in the prior year. The increase of $2.3 million was primarily due to an increase in the CB-839 program, including for Phase 2 start-up activities, as well as investment in our early stage research programs, partially offset by decreases in the CB-1158 program including Incyte’s co-funding of development costs

General and administrative expenses were $2.8 million for the three months ended June 30, 2017, compared with $2.7 million for the same period in the prior year. The increase of $0.1 million was primarily due to increases in professional services and higher personnel-related costs. Net loss from operations for the three months ended June 30, 2017 was $5.2 million, or $0.15 per share.

Conference Call Information

Calithera will host an update conference call today, August 8th at 1:30 p.m. Pacific Time/ 4:30 p.m. Eastern Time. The call can be accessed by dialing (855) 783-2599 (domestic) or (631) 485-4877 (international), and referring to conference ID 63329558. To access the live audio webcast or the subsequent archived recording, visit the Investors section of the Calithera website at www.calithera.com. The webcast will be recorded and available for replay on Calithera’s website for 30 days.

On August 8, 2017 Carna Biosciences presents financial results FY2017 Q2 presentation (Presentation, Carna Biosciences, AUG 8, 2017, View Source [SID1234526909]).

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On August 8, 2017 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the second quarter of 2017 and affirmed financial guidance for 2017 (Press release, Jazz Pharmaceuticals, AUG 8, 2017, View Source;p=RssLanding&cat=news&id=2292679 [SID1234520180]).

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"Thus far, 2017 has been a highly productive year. We have executed on and delivered results of key clinical development programs, advanced multiple global regulatory efforts and received U.S. approval of Vyxeos for the treatment of adults with newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "We continue to invest in our key products, product launches, R&D and corporate development activities to fuel our future growth and create long-term value."

GAAP net income for the second quarter of 2017 was $105.6 million, or $1.72 per diluted share, compared to $114.5 million, or $1.85 per diluted share, for the second quarter of 2016.

Adjusted net income for the second quarter of 2017 was $157.4 million, or $2.56 per diluted share, compared to $165.8 million, or $2.67 per diluted share, for the second quarter of 2016. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release.

Financial Highlights

Three Months Ended
June 30,

Six Months Ended
June 30,

(In thousands, except per share amounts and percentages)
2017

2016

Change

2017

2016

Change
Total revenues
$
394,386

$
381,161

3%

$
770,439

$
717,171

7%

GAAP net income
$
105,604

$
114,502

(8)%

$
192,115

$
190,314

1%

Adjusted net income
$
157,354

$
165,804

(5)%

$
298,576

$
300,372

(1)%

GAAP EPS
$
1.72

$
1.85

(7)%

$
3.13

$
3.05

3%

Adjusted EPS
$
2.56

$
2.67

(4)%

$
4.87

$
4.82

1%

Total Revenues

Three Months Ended
June 30,

Six Months Ended
June 30,
(In thousands)
2017

2016

2017

2016
Xyrem (sodium oxybate) oral solution
$
298,026

$
280,968

$
570,352

$
530,505

Erwinaze / Erwinase (asparaginase Erwinia chrysanthemi)
49,024

49,748

100,412

100,921

Defitelio (defibrotide sodium) / defibrotide
30,238

33,246

66,138

51,143

Prialt (ziconotide) intrathecal infusion
5,656

8,073

13,373

14,282

Other
6,711

7,075

13,058

16,175

Product sales, net
389,655

379,110

763,333

713,026

Royalties and contract revenues
4,731

2,051

7,106

4,145

Total revenues
$
394,386

$
381,161

$
770,439

$
717,171

Net product sales increased 3% in the second quarter of 2017 compared to the same period in 2016 due to higher net product sales of Xyrem.

Xyrem net product sales increased 6% in the second quarter of 2017 compared to the same period in 2016.

Erwinaze/Erwinase net product sales in the second quarter of 2017 were consistent with net product sales in the same period in 2016. During the 2017 quarter, the company continued to experience supply challenges that resulted in temporary supply disruptions in certain markets, which the company expects will continue for the remainder of 2017.

Defitelio/defibrotide net product sales decreased 9% in the second quarter of 2017 compared to the same period in 2016 primarily due to inventory stocking in the second quarter of 2016, following the U.S. launch in that quarter, and the impact of unfavorable foreign exchange rates. The company continues to expect inter-quarter variability in Defitelio net sales given that veno-occlusive disease is an ultra-rare disease.

Operating Expenses

Three Months Ended
June 30,

Six Months Ended
June 30,
(In thousands, except percentages)
2017

2016

2017

2016
GAAP:

Cost of product sales
$
28,672

$
23,980

$
53,737

$
47,419

Gross margin
92.6%

93.7%

93.0%

93.3%

Selling, general and administrative
$
132,328

$
122,618

$
276,583

$
251,383

% of total revenues
33.6%

32.2%

35.9%

35.1%

Research and development
$
40,157

$
39,091

$
85,085

$
70,343

% of total revenues
10.2%

10.3%

11.0%

9.8%

Three Months Ended
June 30,

Six Months Ended
June 30,
(In thousands, except percentages)
2017

2016

2017

2016
Non-GAAP adjusted:

Cost of product sales
$
27,145

$
23,017

$
50,964

$
45,657

Gross margin
93.0%

93.9%

93.3%

93.6%

Selling, general and administrative
$
111,454

$
99,488

$
229,904

$
202,099

% of total revenues
28.3%

26.1%

29.8%

28.2%

Research and development
$
35,298

$
35,562

$
76,084

$
63,524

% of total revenues
9.0%

9.3%

9.9%

8.9%

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 2017 compared to the same period in 2016 on a GAAP and on a non-GAAP adjusted basis due to higher headcount and other expenses resulting from the expansion of the company’s business, the company’s narcolepsy disease awareness campaign and pre-launch activities related to the U.S. launch of VyxeosTM (daunorubicin and cytarabine) liposome for injection.
Research and development (R&D) expenses were consistent on a GAAP and on a non-GAAP adjusted basis in the second quarter of 2017 compared to the same period in 2016. The 2017 quarter included expenses related to regulatory activities for Vyxeos, increased expenses for continued investments in sleep-related R&D programs, an increase in headcount to support these activities and a decrease in costs related to JZP-110 studies for excessive sleepiness associated with obstructive sleep apnea and with narcolepsy due to the completion of three Phase 3 studies.
Cash Flow and Balance Sheet

As of June 30, 2017, cash, cash equivalents and investments were $319.2 million, and the outstanding principal balance of the company’s long-term debt was $1.8 billion. During the six months ended June 30, 2017, the company repaid $350.0 million of borrowings under the company’s revolving credit facility and used $30.9 million to repurchase approximately 230,000 ordinary shares under the company’s share repurchase program at an average cost of $134.10 per ordinary share.

Recent Developments

In June 2017, the company presented positive efficacy results from its global multi-center studies evaluating Xyrem for the treatment of cataplexy in pediatric patients with narcolepsy and JZP-110 in adult patients with excessive sleepiness associated with obstructive sleep apnea and with narcolepsy.

In July 2017, the company entered into a license agreement with XL-protein GmbH (XLp) for the rights to develop, manufacture and commercialize products using XLp’s PASylation technology to extend the plasma half-life of selected asparaginase product candidates.

On August 3, 2017, the U.S. Food and Drug Administration (FDA) approved Vyxeos for the treatment of adults with newly-diagnosed therapy-related AML or AML with myelodysplasia-related changes.

2017 Financial Guidance

Jazz Pharmaceuticals is affirming its full year 2017 financial guidance as follows (in millions, except per share amounts and percentages):

Revenues
$1,625-$1,700
Total net product sales
$1,617-$1,692
-Xyrem net sales
$1,200-$1,230
-Erwinaze/Erwinase net sales
$205-$225
-Defitelio/defibrotide net sales
$130-$150
-Vyxeos net sales
$10-$20
GAAP gross margin %
93%
Non-GAAP adjusted gross margin %1,4
93%
GAAP SG&A expenses
$521-$556
Non-GAAP adjusted SG&A expenses2,4
$440-$460
GAAP R&D expenses
$185-$216
Non-GAAP adjusted R&D expenses3,4
$165-$180
GAAP net income per diluted share
$6.55-$7.55
Non-GAAP adjusted net income per diluted share4
$10.70-$11.30

1.
Excludes $5 million of share-based compensation expense from estimated GAAP gross margin.
2.
Excludes $75-$90 million of share-based compensation expense and $6 million of expenses related to certain legal proceedings and restructuring from estimated GAAP SG&A expenses.
3.
Excludes $20-$25 million of share-based compensation expense and $0-$11 million of milestone payments 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 2017 Net Income Guidance" at the end of this press release.
Conference Call Details

On August 8, 2017 Valeant Pharmaceuticals International, Inc. (NYSE: VRX) (TSX: VRX) ("Valeant" or the "Company" or "we") reported its second-quarter 2017 financial results (Press release, Valeant, AUG 8, 2017, http://ir.valeant.com/news-releases/2017/08-08-2017-120421466 [SID1234520078]).

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"The investments we are making in our core business are delivering results," said Joseph C. Papa, chairman and chief executive officer, Valeant. "The Bausch + Lomb/International segment and Salix business, which together represented 73 percent of our revenue in the quarter, delivered strong organic growth1, and we are continuing to reduce debt and resolve legacy issues."

"Additionally, we confirm that we are maintaining our 2017 full-year Adjusted EBITDA guidance range despite the impact of divestitures we’ve made this year," added Mr. Papa.

Company Highlights

Strengthening the Balance Sheet

Completed sale of Dendreon Pharmaceuticals LLC and used net proceeds to pay down $811 million of senior secured term loans

Announced that Valeant will redeem the remaining $500 million aggregate principal amount of our outstanding 6.75% Senior Notes due 2018, using cash on hand, on Aug. 15, 2017. Upon redemption, the Company expects to:

Have reduced total debt by more than $4.8 billion since the end of the first quarter of 2016

Have no debt maturities and no mandatory amortization requirements until 2020

Announced agreements to sell iNova Pharmaceuticals and Obagi Medical Products businesses for $930 million and
$190 million in cash, respectively; both remain on track to close in the second half of 2017

Generated $268 million and $1.222 billion in cash flow from operations in the second quarter and for the six months that ended June 30, 2017, respectively

Delivered GAAP net loss of $38 million and Adjusted EBITDA (non-GAAP) of $951 million

Achieving positive outcomes in resolving and managing litigation and investigations, including settling the Salix
securities class action litigation

Expects to exceed commitment to pay down $5 billion in debt from divestiture proceeds and free cash flow before February 2018

Executing on Core Businesses

Grew revenue in the Salix business by 13% compared to the second quarter of 2016 and organically grew1 revenue in the Salix business by 16% compared to the second quarter of 2016

XIFAXAN (rifaximin) revenues rose by 16% compared to the second quarter of 2016

Strong XIFAXAN growth, with prescriptions up 6% sequentially and 2% versus the second quarter of 2016, and extended Rx unit volume up 4% versus second quarter of 2016

APRISO (mesalamine) prescriptions grew by 7% compared to the second quarter of 2016

RELISTOR (methylnaltrexone bromide) prescriptions grew by 33% compared to the second quarter of 2016

Revenue of the Bausch + Lomb/International segment decreased by 3% compared to the second quarter of 2016; however, the segment revenue increased organically1 by approximately 6% compared to the second quarter of 2016

Grew revenue in the Bausch + Lomb business in China by 4% compared to the second quarter of 2016 despite currency headwinds and organically grew1 revenue in this business by 9%, compared to the second quarter of 2016, driven by volume

Advanced Bausch + Lomb business

Introduced Bausch + Lomb AQUALOX bi-weekly contact lenses in Japan in June

Introduced Bausch + Lomb renu Advanced Formula multi-purpose contact lens solution

Received filing acceptance from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) for Luminesse2 (brimonidine tartrate ophthalmic solution, 0.025%) with a PDUFA action date of Dec. 27, 2017

Received FDA 510(k) clearances for Vitesse and Stellaris Elite Vision Enhancement System

Continued to focus on stabilizing the dermatology business

Launched SILIQ (brodalumab) injection in July as the lowest-priced injectable biologic for moderate-to-severe plaque psoriasis in the United States

Rebranded the business as Ortho Dermatologics in July

Received FDA filing acceptance for the NDA for PLENVU2 (NER1006), a novel, low volume polyethylene glycol-based bowel preparation for colonoscopies

Second-Quarter Revenue Performance
Total revenues were $2.233 billion for the second quarter of 2017, as compared to $2.420 billion in the second quarter of 2016, a decrease of $187 million, or 8%. The decrease was primarily driven by decreases in volume and price in our U.S. Diversified Products segment, attributed to the previously reported loss of exclusivity for a basket of products, and the dermatology business. The decline also reflects the unfavorable impact of divestitures and discontinuations, primarily the skincare divestiture within the Bausch + Lomb/International segment.3

Revenues by segment for the second quarter of 2017 were as follows:
$ in millions
2017
2016
Reported
Change
Reported
Change
Change at
Constant
Currency4
Organic
Growth1
Segment

Bausch + Lomb/International
$1,241
$1,277
$(36)
(3%)
1%
6%
Branded Rx
$636
$653
$(17)
(3%)
(3%)
0%
U.S. Diversified Products
$356
$490
$(134)
(27%)
(27%)
(27%)
Total Revenues
$2,233
$2,420
$(187)
(8%)
(5%)
(3%)

Bausch + Lomb/International Segment
The Bausch + Lomb/International segment revenues were $1.241 billion for the second quarter of 2017, as compared to $1.277 billion for second quarter of 2016, a decrease of $36 million, or 3%. Excluding the impact of the skincare divestiture and foreign exchange, the Bausch + Lomb/International segment organically grew1 by approximately 6% compared to the second quarter of 2016, driven by performance in China, Europe and Africa/Middle East and the Global Ophthalmology business.

Branded Rx Segment
The Branded Rx segment revenues were $636 million for the second quarter of 2017, as compared to $653 million for second quarter of 2016, a decrease of $17 million, or 3%. The decrease in sales primarily was due to lower volumes in the dermatology business and the impact of divestitures and discontinuations in the Salix business. The decline was largely offset by 13% revenue growth in the Salix business compared to the second quarter of 2016, despite the impact of the divestiture of Ruconest, and organic growth1 in the Salix business of 16% compared to the second quarter of 2016.

U.S. Diversified Products Segment
The U.S. Diversified Products segment revenues were $356 million for the second quarter of 2017, as compared to $490 million for second quarter of 2016, a decrease of $134 million, or 27%. The decline was primarily driven by decreases in volume and price attributed to the previously reported loss of exclusivity for a basket of products.

Operating Income
Operating income was $175 million for the second quarter of 2017 as compared to $81 million for the second quarter of 2016, an increase of $94 million. The increase in operating income primarily reflects lower asset impairments and amortization charges partially offset by a decrease in contribution margin as a result of the decline in product sales from existing businesses.

Net loss for the three months ended June 30, 2017 was $38 million, as compared to $302 million for the same period in 2016, an improvement of $264 million. The decrease in net loss primarily reflects the increase in recovery for income taxes, increase in operating income and the net change in foreign exchange.

Cash provided by operating activities was $268 million for the second quarter of 2017. Cash flows from operations were negatively affected by $190 million of net payments made in resolution of the Salix securities class action litigation.5 Excluding these payments, the Company generated a normalized cash flow of $458 million.
GAAP Earnings Per Share (EPS) Diluted – for the second quarter of 2017 came in at $(0.11) as compared to $(0.88) in the second quarter of 2016.

Adjusted EBITDA(non-GAAP)
Adjusted EBITDA (non-GAAP) was $951 million for the second quarter of 2017, as compared to $1.087 billion for the second quarter of 2016, a decrease of $136 million, primarily due to lower revenues attributed to the previously reported loss of exclusivity for a basket of products, divestitures and discontinuations, and declines in our dermatology business, partially offset by strong organic growth1 in the Bausch + Lomb/International segment and the Salix business. Adjusted EBITDA grew by 10% sequentially versus the prior quarter.

2017 Guidance
Valeant has updated guidance for 2017, as follows:
Full-Year Revenues in the range of $8.70 – $8.90 billion from $8.90 – $9.10 billion
The Company confirms we will maintain our full-year Adjusted EBITDA (non-GAAP) guidance range of $3.60 – $3.75 billion despite the impact of divestitures that have closed in 2017.

This updated guidance reflects the impact of the sale of the CeraVe, AcneFree and AMBI skincare brands and the sale of Dendreon Pharmaceuticals LLC. This guidance does not reflect the impact of the sales of the iNova Pharmaceuticals and Obagi Medical Products businesses, which are both expected to close in the second half of the year.

Other than with respect to GAAP Revenues, the Company only provides guidance on a non-GAAP basis. The Company does not provide a reconciliation of forward-looking Adjusted EBITDA (non-GAAP) to GAAP net income (loss), due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation. In periods where significant acquisitions or divestitures are not expected, the Company believes it might have a basis for forecasting the GAAP equivalent for certain costs, such as amortization, which would otherwise be treated as non-GAAP to calculate projected GAAP net income (loss). However, because other deductions (such as restructuring, gain or loss on extinguishment of debt and litigation and other matters) used to calculate projected net income (loss) vary dramatically based on actual events, the Company is not able to forecast on a GAAP basis with reasonable certainty all deductions needed in order to provide a GAAP calculation of projected net income (loss) at this time. The amount of these deductions may be material and, therefore, could result in projected GAAP net income (loss) being materially less than projected Adjusted EBITDA (non-GAAP).

Additional Highlights
Valeant’s cash, cash equivalents and restricted cash were $2.025 billion at June 30, 2017
The Company’s availability under the Revolving Credit Facility was approximately $930 million at June 30, 2017
Valeant’s corporate credit ratings remained unchanged during the second quarter of 2017
John Paulson, president of Paulson & Co., Inc., a New York-based investment firm, joined the Company’s Board of Directors

On August 8, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported financial results for the second quarter 2017 and commented on recent accomplishments and clinical development plans for its lead, novel, oral Selective Inhibitor of Nuclear Export (SINE) compound selinexor (KPT-330), and other pipeline assets verdinexor (KPT-335), and KPT-9274, its oral, dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT) (Filing, Q2, Karyopharm, 2017, AUG 8, 2017, View Source [SID1234520182]).

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"Our second quarter achievements marked significant progress across several of our development programs, and especially for selinexor," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "At the 2017 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, we reported updated data from the Phase 2b SADAL study investigating selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The overall response rate (ORR) increased to 33.3% for the overall trial population with similar response rates in patients with double- or triple-hit DLBCL, indicating clear activity in this population which usually has a particularly poor prognosis. As we move to the second half of the year, our focus remains on execution of key later-stage trials in our lead indications of multiple myeloma (MM), DLBCL and liposarcoma. In myeloma, the pivotal Phase 3 BOSTON study is now underway. The Phase 2b STORM study, for possible accelerated approval, continues to enroll well with top-line data expected by April 2018. In liposarcoma, the Phase 2 portion of the blinded, randomized Phase 2/3 SEAL study recently completed enrollment and we look forward to reporting the hazard ratio for progression-free survival (PFS) and providing an update regarding the planned development path in this indication during September or October 2017."

Second Quarter 2017 and Recent Events, Highlights and Milestones:

Selinexor in Multiple Myeloma

Pivotal Phase 3 BOSTON Study Initiated. Karyopharm initiated the pivotal, randomized Phase 3 BOSTON (Bortezomib, Selinexor and dexamethasone) study, evaluating once weekly selinexor 100mg in combination with the proteasome inhibitor Velcade (bortezomib, once weekly) and dexamethasone (SVd), compared to standard dose Velcade (twice weekly) and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. The primary endpoints of the study are PFS and ORR. The BOSTON study is expected to enroll approximately 360 patients at over 100 clinical sites internationally. Karyopharm is projecting to complete enrollment in 2018, with top-line data anticipated in 2019.

Selinexor Named Among the "Top 5 Oncology R&D Products Worldwide in 2022" by EvaluatePharma. In EvaluatePharma’s recent report, World Preview 2017, Outlook to 2022, selinexor was projected to be one of the top five selling oncology research and development products worldwide in 2022, with the potential to generate estimated revenues of $920 million in worldwide annual sales and capture 0.5% of the worldwide oncology market share in the same timeframe. This analysis is based on EvaluatePharma’s coverage of the world’s 6,500 leading pharmaceutical and biotech companies and highlights certain important industry trends by therapy area.

Ongoing Phase 2b STORM Study Expansion in Patients with Penta-refractory MM. The Phase 2b STORM study, which was recently expanded to include 122 additional patients with penta-refractory MM, continues to enroll on track. Karyopharm expects to report top-line data from the expanded cohort by April 2018, and, assuming a positive outcome, intends to use the data from the expanded STORM study to support a request for accelerated approval for selinexor in heavily pretreated MM.

Ongoing Phase 1b/2 STOMP Study Evaluating Selinexor in Combination with Several Key MM Drugs. Enrollment is complete in the Phase 1b/2 STOMP arm evaluating selinexor in combination with Velcade and low-dose dexamethasone (SVd) in heavily pretreated patients with MM. The SVd arm of the STOMP study enrolled 42 patients. Dose escalation is complete and expansion is ongoing in the arms evaluating oral selinexor plus immunomodulatory drug (IMID) combinations, including selinexor + Revlimid (lenalidomide) + dexamethasone (SRd), and selinexor + Pomalyst (pomalidomide) and dexamethasone (SPd). The Company expects to report updated data on these convenient, all oral regimens by year end 2017.

New Study Arm Initiated in Phase 1b/2 STOMP Study Evaluating Selinexor in Combination with Darzalex (daratumumab). Karyopharm has dosed patients in a new Phase 1b/2 STOMP study arm designed to evaluate selinexor in combination with the anti-CD38 monoclonal antibody Darzalex and low-dose dexamethasone (SDd) in heavily pretreated patients with MM. The SDd arm of the STOMP study is expected to enroll up to 16 patients and the Company expects to report top-line data in the first half of 2018.
Selinexor in Diffuse Large B-Cell Lymphoma

Updated Data from Phase 2b SADAL Study in DLBCL Presented at EHA (Free EHA Whitepaper) 2017. At the 2017 EHA (Free EHA Whitepaper) Annual Meeting in June, an oral presentation was given that highlighted updated data from the ongoing Phase 2b SADAL study evaluating single-agent selinexor in patients with relapsed or refractory DLBCL. This latest data demonstrated that selinexor achieved an ORR of 33.3% and a duration of response (DOR) of > 7 months in the first 63 patients, as adjudicated by an independent central radiological committee. Patients were randomized to one of two single-agent selinexor arms, a higher dose arm of 100 mg twice weekly and a lower dose arm of 60 mg twice weekly. The median overall survival was 8 months for all patients, consistent with published data in this population which has a very poor prognosis. As of the data cutoff date, the median survival for the responders had not been reached and was over 9 months. Most responses occurred at the first response evaluation (~2 months). As of the data cutoff date, 9 of the 21 responding patients remained on treatment, including 6 patients who had a complete response (CR). Selinexor also showed robust, single-agent activity against GCB and non-GCB subtypes of DLBCL. Of the 32 patients with DLBCL of the GCB-subtype, 9 responded (4 patients with a CR, 5 patients with a partial response (PR)) for an ORR of 28.1%. Of the 31 patients with DLBCL of the non-GCB (or ABC)-subtype, 12 responded (5 patients with a CR, 7 patients with a PR) for an ORR of 38.7%. Amongst the 14 patients with "double-" or "triple-hit" DLBCL, the ORR was consistent with the ORR across the SADAL patient population, indicating anti-cancer activity in this population, which usually has a particularly poor prognosis. Side effects were consistent with those previously reported with selinexor, and no new safety signals were identified. Importantly, side effects were reduced in the 60mg cohort in comparison with the 100mg cohort.

In consultation with the U.S. Food and Drug Administration (FDA), Karyopharm amended the SADAL study, removing the 100mg arm and continuing enrollment only in the 60mg twice weekly arm. The FDA has agreed that the single-arm trial design appears appropriate for accelerated approval in DLBCL, though eligibility for accelerated approval will depend on the complete trial results and available therapies at the time of regulatory action. The SADAL study is expected to enroll up to a total of 130 patients in the 60mg single-arm cohort and Karyopharm plans to report top-line results in the second half of 2018.
Selinexor in Other Hematologic Malignancies

Published Phase 1 Data Demonstrating Selinexor’s Activity in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma (NHL) in the Journal Blood. A paper describing results from the first in human Phase 1 clinical study assessing safety and preliminary activity of selinexor in patients with relapsed or refractory NHL was recently published in the journal Blood. In the paper, authored by John Kuruvilla, et al., titled "Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin’s lymphoma," Karyopharm collaborators reported that selinexor was generally well tolerated. Of the 70 evaluable patients, 22 (31%) achieved an objective response (OR), including 4 CRs and 18 PRs, which were observed across a spectrum of NHL subtypes, including DLBCL, Richter’s transformation, mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. All four CRs were in patients with DLBCL, and two of the four patients are believed to have remained relapse-free as of the publication date, greater than 3 years since initiation of single agent selinexor therapy. Tumor biopsies showed decreases in cell signaling pathways, reduced proliferation, nuclear localization of XPO1 cargos and increased apoptosis after treatment. The most common grade 3-4 drug-related AEs were thrombocytopenia (47%), neutropenia (32%), anemia (27%), leukopenia (16%), fatigue (11%) and hyponatremia (10%). A maximum tolerated dose was not defined, but the highest allowable dose was ~120 mg twice weekly. Based on both tolerability and antitumor activity, the recommended Phase 2 dose of selinexor in NHL is 35 mg/m2 (~60 mg) twice weekly.

Selinexor in Solid Tumors

Ongoing Phase 2/3 SEAL Study in Liposarcoma. Enrollment is now complete in the Phase 2 portion of the blinded, randomized Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with advanced liposarcoma. Karyopharm expects to report the hazard ratio for PFS from the Phase 2 portion of the SEAL study and providing an update regarding the planned development path in this indication during September or October 2017. The primary endpoint of the SEAL study is PFS and both the trial design and endpoints have been accepted by the FDA and the European Medicines Agency.

Oral Presentation Highlighting Efficacy, Safety and Intratumoral Pharmacokinetic Data for Selinexor in Glioblastoma at the 2017 World Federation of Neuro-Oncology Societies (WFNOS) Meeting. Clinical data from a Phase 2 study evaluating selinexor in patients with recurrent glioblastoma was highlighted in an oral presentation at the 2017 WFNOS meeting by Andrew Lassman, MD, Columbia University Medical Center. The data demonstrated that oral selinexor achieved responses and sufficient intratumoral penetration, with a manageable tolerability profile when accompanied by standard supportive care. Importantly, disease control rates using selinexor dosed at 80 mg once weekly were as high or higher than those observed with more intensive dosing, and tolerability was improved.
Verdinexor

Signed Global License Agreement with Anivive Lifesciences for Verdinexor for Animal Health Applications. Karyopharm and Anivive, a privately-held biotech company, executed a licensing agreement under which Anivive licensed from Karyopharm exclusive worldwide rights to research, develop and commercialize verdinexor for the treatment of cancer in companion animals. Under the terms of the agreement, Anivive made a one-time upfront payment of $1 million to Karyopharm. Anivive also agreed to pay up to an additional $43.5 million based on technology transfer and achievement of specified regulatory, clinical and commercial milestones, assuming approval in both the U.S. and the European Union. In addition, Anivive agreed to pay Karyopharm a low double-digit royalty based on future net sales of verdinexor.
KPT-9274

Preclinical Efficacy Highlighting KPT-9274’s Anti-Cancer Activity in Dogs with Spontaneous Lymphomas Presented as a Late-Breaking Poster at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2017 Annual Meeting. At the AACR (Free AACR Whitepaper) 2017 Annual Meeting in April, Karyopharm collaborator Cheryl London of Tufts University presented a late-breaking poster highlighting preclinical data demonstrating the activity and synergy of KPT-9274, the Company’s oral dual inhibitor of PAK4/NAMPT, with doxorubicin to treat dogs with lymphoma. KPT-9274 is currently being evaluated in a Phase 1 safety and tolerability study in patients with advanced solid malignancies (including sarcoma, colon and lung cancer) or non-Hodgkin’s lymphoma (NHL) whose disease has relapsed after standard therapy(s). Top-line data from this clinical study are expected later this year.
Other Corporate and Clinical Developments

Generated $52.3 Million in Equity Financings. In April 2017, the Company sold approximately 3.9 million shares of common stock in an underwritten public offering at a price to the public of $10.25 per share, resulting in net proceeds to the Company of approximately $37.9 million after deducting underwriting discounts and commissions and other offering expenses, and sold approximately 1.3 million shares under its ATM offering facility for net proceeds of approximately $14.4 million.
Second Quarter 2017 Financial Results

Cash, cash equivalents and investments as of June 30, 2017, including restricted cash, totaled $181.2 million, compared to $175.5 million as of December 31, 2016.

On April 28, 2017, Karyopharm completed an underwritten public offering of 3,902,439 shares of its common stock at a price to the public of $10.25 per share. The net proceeds to Karyopharm from the offering, after deducting the underwriting discounts and commissions and offering expenses, were approximately $37.9 million. In addition, during April 2017, the Company sold approximately 1.3 million shares under its ATM offering facility for net proceeds of approximately $14.4 million.

For the quarter ended June 30, 2017, research and development expense was $23.1 million compared to $24.6 million for the quarter ended June 30, 2016. For the quarter ended June 30, 2017, general and administrative expense was $6.6 million compared to $6.0 million for the quarter ended June 30, 2016.

Karyopharm reported a net loss of $29.4 million, or $0.64 per share, for the quarter ended June 30, 2017, compared to a net loss of $30.2 million, or $0.84 per share, for the quarter ended June 30, 2016. Net loss includes stock-based compensation expense of $5.1 million and $6.4 million for the quarters ended June 30, 2017 and June 30, 2016, respectively.