On October 30, 2017 Acorda Therapeutics, Inc. (Nasdaq:ACOR) provided a financial and pipeline update for the third quarter ended September 30, 2017 (Press release, Acorda Therapeutics, OCT 31, 2017, View Source [SID1234521332]).

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 had a constructive dialogue with the FDA since the issuance of its Refusal to File letter, and we plan to resubmit the INBRIJA NDA in the fourth quarter. We believe our resubmission reflects a strong package that incorporates feedback we received from FDA,” said Ron Cohen, M.D., Acorda’s President and CEO. “We are also on track to announce top-line data from our Phase 3 study of tozadenant in the first quarter of 2018.”

“INBRIJA and tozadenant are being developed as therapies for people with Parkinson’s, INBRIJA for on-demand use to treat symptoms of OFF periods and tozadenant as a daily oral treatment to increase overall ON time. If approved, they have the potential to position Acorda as a leader in the development of Parkinson’s therapy, creating substantial value for shareholders.”

Third Quarter 2017 Financial Results

AMPYRA (dalfampridine) Extended Release Tablets, 10 mg – For the quarter ended September 30, 2017, the Company reported AMPYRA net revenue of $132.6 million compared to $128.8 million for the same quarter in 2016.

FAMPYRA (prolonged-release fampridine tablets) – For the quarter ended September 30, 2017, the Company reported FAMPYRA royalties from sales outside of the U.S. of $3.1 million compared to $2.6 million for the same quarter in 2016.

Research and development (R&D) expenses for the quarter ended September 30, 2017 were $33.3 million, including $2.0 million of share-based compensation and $.03 million of restructuring expenses compared to $54.8 million, including $2.9 million of share-based compensation, for the same quarter in 2016.

Sales, general and administrative (SG&A) expenses for the quarter ended September 30, 2017 were $40.7 million, including $4.6 million of share-based compensation and $0.01 million of restructuring expenses compared to $54.4 million, including $7.1 million of share-based compensation for the same quarter in 2016.

The Company recorded a non-cash intangible asset impairment charge of $39.4 million in the quarter ended September 30, 2017 for Selincro. Selincro is currently marketed in Europe by the licensor for the reduction of alcohol consumption in alcohol dependent adults. The Company re-assessed its valuation assumptions, including expected future growth related to the expansion into new markets, and determined that the intangible asset was impaired.

Provision for income taxes for the quarter ended September 30, 2017 was $18.9 million, including $3.7 million of cash taxes, compared to a provision for income taxes of $3.0 million, including $1.0 million of cash taxes, for the same quarter in 2016.

The Company reported a GAAP net loss attributable to Acorda of $(25.2) million for the quarter ended September 30, 2017, or $(0.55) per diluted share. GAAP net loss in the same quarter of 2016 was $(12.7) million, or $(0.28) per diluted share.

Non-GAAP net income for the quarter ended September 30, 2017 was $20.1 million, or $0.43 per diluted share. Non-GAAP net loss in the same quarter of 2016 was $(1.9) million, or $(0.04) per diluted share. This quarterly non-GAAP net income measure, more fully described below under “Non-GAAP Financial Measures,” excludes share-based compensation charges, non-cash interest charges on our debt, restructuring expenses, changes in the fair value of acquired contingent consideration, intangible asset impairment charges and acquisition-related expenses. A reconciliation of the GAAP financial results to non-GAAP financial results is included with the attached financial statements.

At September 30, 2017, the Company had cash and cash equivalents of $192.5 million.

Guidance for 2017

The Company reiterates AMPYRA 2017 net revenue of $535-$545 million.
R&D expenses for the full year 2017 are expected to be $160-$170 million. This guidance is a non-GAAP projection that excludes share-based compensation and restructuring costs, as more fully described below under “Non-GAAP Financial Measures.”
The Company is reducing its SG&A expense guidance for the full year 2017 from $170-$180 million to $160-$170 million. This guidance is a non-GAAP projection that excludes share-based compensation and restructuring costs, as more fully described below under “Non-GAAP Financial Measures.”
The Company expects to be cash flow positive in 2017, with a projected year-end cash balance in excess of $200 million.
Third Quarter 2017 Highlights

INBRIJA (levodopa inhalation powder) in Parkinson’s disease
In August, the Company received a Refusal to File (RTF) letter regarding its NDA for INBRIJA. After constructive dialogue with the FDA, the Company expects to resubmit the NDA in Q4 2017.
As a result, the Company has revised the timing for its end-of-year submission of the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) to Q1 2018.
INBRIJA is an investigational treatment for symptoms of OFF periods in people with Parkinson’s disease taking a carbidopa/levodopa regimen.
Tozadenant in Parkinson’s disease
The Company expects to report topline Phase 3 in Q1 2018.
Tozadenant is an investigational treatment for the reduction of OFF time in people with Parkinson’s disease.
AMPYRA (dalfampridine)
The Company filed its opening brief for its appeal to the U.S. Court of Appeals for the Federal Circuit of the District Court’s decision in the AMPYRA patent litigation. The defendants have filed their opposition and cross-appeal opening brief. Reply briefs from both parties are expected to be filed in November 2017, followed by oral argument to be scheduled by the appellate court.
Both BIO and PhRMA filed amicus briefs in support of the Company’s appeal, raising important issues in conjunction with biopharmaceutical innovation.
The Company expects to maintain exclusivity of AMPYRA at least through July 2018.
Webcast and Conference Call

The Company will host a conference call today at 8:30 a.m. ET. To participate, please dial (844) 579-6824 (domestic) or (763) 488-9145 (international) and reference the access code 95686626. A replay of the call will be available from 11:30 a.m. ET on October 31, 2017 until 2:59 p.m. ET on November 30, 2017. To access the replay, please dial (855) 859-2056 (domestic) or (404) 537-3406 (international) and reference the access code 95686626. The archived webcast will be available in the Investor Relations section of the Acorda website at www.acorda.com.On October 30, 2017

On October 31, 2017 AstraZeneca and MedImmune, its global biologics research and development arm, reported the expansion of their clinical collaboration with Incyte Corporation (Press release, AstraZeneca, OCT 31, 2017, View Source [SID1234521325]). As part of the agreement, the companies will evaluate the efficacy and safety of epacadostat, Incyte’s investigational selective IDO1 enzyme inhibitor, in combination with AstraZeneca’s Imfinzi (durvalumab), a human monoclonal antibody directed against PD-L1, compared to Imfinzi alone.

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!

The exclusive collaboration for the study population allows for the two companies to conduct a Phase III trial in patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) whose disease has not progressed following platinum-based chemotherapy concurrent with radiation therapy (CRT).

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "Imfinzi has shown exciting clinical potential in treating patients with locally-advanced lung cancer. We are pleased to build on recent data from the PACIFIC trial to further explore how Imfinzi, in combination with an IDO inhibitor could provide additional benefit to patients with locally-advanced lung cancer."

Steven Stein, MD, Chief Medical Officer, Incyte, said: "We are pleased to expand our ongoing clinical collaboration with AstraZeneca and to further explore the potential of epacadostat in patients with locally-advanced unresectable lung cancer. We look forward to beginning an additional pivotal trial for epacadostat, as we seek to position IDO1 enzyme inhibition as a key component of combination immunotherapy."

The Phase III trial, which will be co-funded by the two companies and will be conducted by AstraZeneca, is expected to begin enrolling patients in the first half of 2018. This agreement builds on an existing clinical collaboration for Imfinzi and epacadostat announced by both companies in May 2014.

NOTES TO EDITORS

About Locally-Advanced (Stage III) NSCLC

Stage III lung cancer is divided into two stages (IIIA and IIIB), which are defined by how much the cancer has spread locally and the possibility of surgery.

Stage III lung cancer represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in seven leading markets[1] in 2016. More than half of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.

About Epacadostat (INCB024360)

The immunosuppressive effects of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity on the tumour microenvironment help cancer cells evade immunosurveillance. Epacadostat is an investigational, highly-potent and selective oral inhibitor of the IDO1 enzyme. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck and bladder cancer. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitors pembrolizumab or nivolumab improved response rates compared with studies of the immune checkpoint inhibitors alone.

On October 31, 2017 Incyte Corporation (Nasdaq: INCY) reported 2017 third-quarter financial results, highlighting 38 percent year-on-year growth in product-related revenue, driven by increased sales of Jakafi (ruxolitinib) in the U.S. and Iclusig (ponatinib) in Europe, and royalties from ex-U.S. sales of Jakavi (ruxolitinib) by Novartis and Olumiant (baricitinib) by Lilly (Press release, Incyte, OCT 31, 2017, View Source [SID1234521336]).

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 exit the third quarter of 2017 with excellent momentum across the whole business," stated Hervé Hoppenot, Incyte’s Chief Executive Officer. "Jakafi and Iclusig continue to outperform our expectations, and we are now evaluating ten different indications across our five late-stage development candidates. We are also on track to initiate the next wave of pivotal trials planned for the epacadostat development program. We are striving to build Incyte into a world-class biopharmaceutical company, and we are very pleased to report another quarter of significant progress towards that goal."

Know more, wherever you are:
Latest on Incyte’s Cancer Pipeline, book your free 1stOncology demo here.

Portfolio Update
Cancer – Targeted Therapies
The REACH1 pivotal trial studying ruxolitinib in patients with steroid-refractory acute graft-versus-host disease (GVHD) is on track to deliver results in the first half of 2018. If successful, Incyte anticipates submitting an sNDA seeking accelerated approval of ruxolitinib in this indication during 2018. Three additional pivotal trials are evaluating the role of JAK inhibition in GVHD (REACH2 and REACH3 with ruxolitinib, and GRAVITAS-301 with itacitinib).
The FIGHT and CITADEL programs evaluating INCB54828 (FGFR1/2/3) and INCB50465 (PI3Kδ), respectively, now include multiple different indications in potentially-pivotal trials.

Indication

Status Update
Ruxolitinib (JAK1/JAK2)
Steroid-refractory acute GVHD Pivotal Phase 2 (REACH1) and Phase 3 (REACH2)
Ruxolitinib (JAK1/JAK2)
Steroid-refractory chronic GVHD Phase 3 (REACH3)
Ruxolitinib (JAK1/JAK2)
Essential thrombocythemia Pivotal Phase 2 (RESET-272) open for enrollment
Itacitinib (JAK1)
Treatment-naïve acute GVHD Phase 3 (GRAVITAS-301)
Itacitinib (JAK1)
Non-small cell lung cancer Phase 1/2 in combination with osimertinib (EGFR)
INCB52793 (JAK1)
Advanced malignancies Phase 1/2 dose-escalation
INCB50465 (PI3Kδ)
Diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma Phase II (CITADEL-202 initiated; CITADEL-203, CITADEL-204, CITADEL-205 all open for enrollment)
INCB54828 (FGFR1/2/3)
Bladder cancer, cholangiocarcinoma; 8p11 MPNs
Phase 2 (FIGHT-201, FIGHT-202, FIGHT-203)
INCB57643 (BRD)
Advanced malignancies Phase 1/2 dose-escalation
INCB53914 (PIM)
Advanced malignancies Phase 1/2 dose-escalation
INCB59872 (LSD1)
Acute myeloid leukemia, small cell lung cancer Phase 1/2 dose-escalation
INCB62079 (FGFR4)
Hepatocellular carcinoma Phase 1/2 dose-escalation

Cancer – Immune Therapies
The pivotal Phase 3 ECHO-301 trial of epacadostat plus pembrolizumab in patients with unresectable or metastatic melanoma is now fully-recruited and data are expected in the first half of 2018.
In collaboration with Merck and Bristol-Myers Squibb, preparations for the next wave of eight pivotal Phase 3 trials of epacadostat plus PD-1 antagonists continue as planned. Initiation of these trials are expected before the end of 2017.

In October, Incyte and AstraZeneca announced an expanded clinical trial collaboration and the companies intend to initiate a Phase 3 trial of epacadostat in combination with AstraZeneca’s PD-L1 antagonist durvalumab in patients with Stage III non-small cell lung cancer.
In October, Incyte and MacroGenics announced an exclusive global collaboration and license agreement for MacroGenics’ MGA012, an investigational monoclonal antibody that inhibits PD-1. Under this agreement, Incyte will obtain exclusive worldwide rights for the development and commercialization of MGA012 in all indications.

Indication

Status Update
Epacadostat (IDO1)
Unresectable or metastatic melanoma Phase 3 (ECHO-301) in combination with pembrolizumab (PD-1)
Epacadostat (IDO1)
NSCLC, renal, bladder and head & neck cancer Phase 3 in combination with pembrolizumab (PD-1) expected to begin in 2017
Epacadostat (IDO1)
NSCLC, head & neck cancer Phase 3 in combination with nivolumab (PD-1) expected to begin in 2017
Epacadostat (IDO1)
NSCLC Phase 3 in combination with durvalumab (PD-L1) expected to begin in H1 2018
Epacadostat (IDO1)
Multiple tumor types Phase 2 (ECHO-202) expansion cohorts in combination with pembrolizumab (PD-1)
Epacadostat (IDO1)
Multiple tumor types Phase 2 (ECHO-204) expansion cohorts in combination with nivolumab (PD-1)
Epacadostat (IDO1)
Multiple tumor types Phase 2 (ECHO-203) expansion cohorts in combination with durvalumab (PD-L1)
INCB01158 (ARG)1
Solid tumors Phase 1/2
INCSHR1210 (PD-1)2
Solid tumors Phase 1/2; enrollment halted
INCAGN1876 (GITR)3
Solid tumors Phase 1/2
INCAGN1949 (OX40)3
Solid tumors Phase 1/2
PD-1 platform study
Solid tumors Phase 1/2, pembrolizumab (PD-1) in combination with itacitinib (JAK1) or INCB50465 (PI3Kδ)
JAK1 platform study
Solid tumors Phase 1/2, itacitinib (JAK1) in combination with epacadostat (IDO1) or INCB50465 (PI3Kδ)

Notes:
1) INCB01158 co-developed with Calithera
2) INCSHR1210 licensed from Hengrui
3) INCAGN1876 & INCAGN1949 from discovery alliance with Agenus

Non-oncology


Indication

Status Update
Topical ruxolitinib (JAK1/JAK2)
Atopic dermatitis, vitiligo Phase 2

Partnered
In August, Lilly and Incyte announced that Lilly plans to resubmit the New Drug Application (NDA) for baricitinib to the U.S. Food & Drug Administration (FDA) before the end of January 2018. The companies anticipate the FDA will classify the application as a Class II resubmission, which would start a new six-month review cycle.
In September, Lilly and Incyte announced that baricitinib met the primary endpoint in a Phase 2 study in patients with moderate-to-severe atopic dermatitis.
Novartis has stated that it anticipates submitting an NDA for capmatinib, a potent and selective c-MET inhibitor licensed from Incyte, in 2018.

Indication

Status Update
Baricitinib (JAK1/JAK2)1
Rheumatoid arthritis Approved in Europe and Japan; CRL issued by FDA
Baricitinib (JAK1/JAK2)1
Psoriatic arthritis Lilly expects the Phase 3 program to begin in 2018
Baricitinib (JAK1/JAK2)1
Atopic dermatitis Lilly expects the Phase 3 program to begin in late 2017
Baricitinib (JAK1/JAK2)1
Systemic lupus erythematosus Phase 2
Capmatinib (c-MET)2
Non-small cell lung cancer, liver cancer Phase 2 in EGFR wild-type ALK negative NSCLC patients with c-MET amplification and mutation

Notes:
1) Baricitinib licensed to Lilly
2) Capmatinib licensed to Novartis

2017 Third-Quarter Financial Results
Revenues For the quarter ended September 30, 2017, net product revenues of Jakafi were $304 million as compared to $224 million for the same period in 2016, representing 36 percent growth. For the nine months ended September 30, 2017, net product revenues of Jakafi were $831 million as compared to $615 million for the same period in 2016, representing 35 percent growth. For the quarter ended September 30, 2017, net product revenues of Iclusig were $18 million as compared to $13 million for the same period in 2016, representing 42 percent growth. For the nine months ended September 30, 2017, net product revenues of Iclusig were $47 million as compared to $17 million for the same period in 20161.

For the quarter and nine months ended September 30, 2017, product royalties from sales of Jakavi, which has been out-licensed to Novartis outside of the United States, were $41 million and $104 million, respectively, as compared to $30 million and $77 million for the same periods in 2016. For the quarter and nine months ended September 30, 2017, product royalties from sales of Olumiant outside of the United States received from Lilly were $3 million, and $4 million, respectively.

For the quarter and nine months ended September 30, 2017, contract revenues were $15 million and $105 million, respectively, as compared to $3 million and $70 million for the same periods in 2016. The contract revenues in 2017 relate to milestone payments earned.

For the quarter ended September 30, 2017, total revenues were $382 million as compared to $269 million for the same period in 2016. For the nine months ended September 30, 2017, total revenues were $1.1 billion as compared to $779 million for the same period in 2016.
1 In June 2016, Incyte obtained an exclusive license from ARIAD to develop and commercialize Iclusig in Europe and other select ex-U.S. countries.

Year Over Year Revenue Growth
(in thousands, unaudited)

Three Months Ended Nine Months Ended
September 30, % September 30, %
2017 2016 Change 2017 2016 Change
Revenues:
Jakafi net product revenues $ 303,929 $ 223,892
36%

$ 831,044 $ 615,285
35%

Iclusig net product revenues
18,100 12,731
42%

47,459 16,721 -
Product royalty revenues 44,487 29,626
50%

108,477 77,486
40%

Product-related revenues 366,516 266,249
38%

986,980 709,492
39%

Contract revenues 15,000 3,214 - 105,000 69,643 -
Other revenues
18 6 - 80 86 -
Total revenues $ 381,534 $ 269,469
42%

$ 1,092,060 $ 779,221
40%

Research and development expenses Research and development expenses for the quarter and nine months ended September 30, 2017 were $270 million and $879 million, respectively, as compared to $143 million and $420 million for the same periods in 2016. The increase in research and development expenses was primarily due to the expansion of the Company’s clinical portfolio as well as upfront and milestone expenses of $209 million related to our collaboration and license agreements with Agenus, Calithera and Merus. Included in research and development expenses for the quarter and nine months ended September 30, 2017 were non-cash expenses related to equity awards to our employees of $23 million and $68 million, respectively.

Selling, general and administrative expenses Selling, general and administrative expenses for the quarter and nine months ended September 30, 2017 were $91 million and $269 million, respectively, as compared to $76 million and $207 million for the same periods in 2016. Increased selling, general and administrative expenses were driven primarily by additional costs related to the commercialization of Jakafi and the geographic expansion in Europe. Included in selling, general and administrative expenses for the quarter and nine months ended September 30, 2017 were non-cash expenses related to equity awards to our employees of $12 million and $31 million, respectively.

Change in fair value of acquisition-related contingent consideration The change in fair value of acquisition-related contingent consideration for the quarter and nine months ended September 30, 2017 was a benefit of $16 million and $2 million, respectively, as compared to expense of $8 million and $10 million for the same periods in 2016. The change in fair value of acquisition-related contingent consideration represents the fair market value adjustments of the Company’s contingent liability related to the acquisition of the European business of ARIAD Pharmaceuticals, Inc.
Unrealized gain (loss) on long term investments Unrealized gain on long term investments for the quarter ended September 30, 2017 was $23 million as compared to $24 million for the same period in 2016. The unrealized loss on long term investments for the nine months ended September 30, 2017 was $2 million as compared to an unrealized gain of $20 million for the same period in 2016. The unrealized gain or loss on long term investments for the quarter and nine months ended September 30, 2017 represents the fair market value adjustments of the Company’s investments in Agenus and Merus.

Expense related to senior note conversions Expense related to senior note conversions for the nine months ended September 30, 2017 was $55 million related to the conversions of certain of our 2018 and 2020 convertible senior notes.

Net income (loss) Net income for the quarter ended September 30, 2017 was $36 million, or $0.17 per basic and diluted share, as compared to net income of $37 million, or $0.20 per basic and $0.19 per diluted share for the same period in 2016. Net loss for the nine months ended September 30, 2017 was $164 million, or $0.81 per basic and diluted share, as compared to net income of $95 million, or $0.51 per basic and $0.49 per diluted share for the same period in 2016.

Cash, cash equivalents and marketable securities position As of September 30, 2017, cash, cash equivalents and marketable securities totaled $1.3 billion as compared to $809 million as of December 31, 2016. The increase in cash, cash equivalents and marketable securities from December 31, 2016 to September 30, 2017 is primarily due to the recent public offering of 4,945,000 shares of our common stock resulting in net proceeds of $649 million.
2017 Financial Guidance

The Company has updated its full year 2017 financial guidance, as detailed below.

Current

Previous
Jakafi net product revenues $1,125-$1,135 million $1,090-$1,120 million
Iclusig net product revenues $60-$65 million Unchanged
Research and development expenses* $1,250-$1,300 million $1,050-$1,150 million
Selling, general and administrative expenses $340-$360 million Unchanged
Change in fair value of acquisition-related contingent consideration $5-$7 million $30-$35 million

* Includes upfront and milestone expenses of $359 million related to the amended Agenus collaboration, and the Merus, Calithera, and MacroGenics collaborations

Conference Call and Webcast Information

Incyte will hold its 2017 third-quarter financial results conference call and webcast this morning at 10:00 a.m. ET. To access the conference call, please dial 877-407-3042 for domestic callers or 201-389-0864 for international callers. When prompted, provide the conference identification number, 13672268.
If you are unable to participate, a replay of the conference call will be available for 30 days. The replay dial-in number for the United States is 877-660-6853 and the dial-in number for international callers is 201-612-7415. To access the replay you will need the conference identification number, 13672268.
The conference call will also be webcast live and can be accessed at www.incyte.com in the Investors section under "Events and Presentations".

On October 31, 2017 Array BioPharma Inc. (Nasdaq: ARRY), a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule cancer therapies, reported results for its first quarter of fiscal 2018 and provided an update on the progress of its key clinical development programs (Press release, Array BioPharma, OCT 31, 2017, View Source [SID1234521349]).

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!

COLUMBUS PHASE 3 TRIAL: Binimetinib and encorafenib submissions under review at FDA and EMA
In September 2017, the FDA accepted for review Array’s NDAs to support use of the combination of binimetinib 45 mg twice daily and encorafenib 450 mg once daily (COMBO450) for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The FDA set a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. In addition, the FDA informed Array that, based on its preliminary review of the applications, it has not identified any potential review issues, and that it is not currently planning to hold an advisory committee meeting to discuss these NDAs. Array completed its NDA submissions based on findings from the pivotal Phase 3 COLUMBUS trial.

“We look forward to supporting the FDA and EMA reviews of the submissions for binimetinib and encorafenib,” said Ron Squarer, Chief Executive Officer. “The robust progression free survival benefit together with the attractive tolerability profile demonstrated in COLUMBUS suggest the combination represents a potentially important addition to the MEK/BRAF treatment landscape for patients with BRAF-mutant melanoma. We continue to build our team to support potential commercialization in 2018.”

Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates[1-2]. There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma[1, 3, 4].

Binimetinib and encorafenib are investigational medicines and are not currently approved in any country.

BEACON CRC PHASE 3 TRIAL: Promising results from safety lead-in presented at 2017 ESMO (Free ESMO Whitepaper)
Array continues to enroll BEACON CRC, a global Phase 3 trial of encorafenib and Erbitux (cetuximab), an anti-EGFR antibody, with or without binimetinib, versus standard of care in patients with BRAF-mutant colorectal cancer (CRC) who have previously received first- or second-line systemic therapy. BRAF-mutant CRC represents a difficult-to-treat subtype of colorectal cancer that impacts 10 to 15% of CRC patients.

At the 2017 ESMO (Free ESMO Whitepaper) Congress held during the quarter, safety results and initial clinical activity were presented from the safety lead-in of the Phase 3 BEACON CRC study evaluating the triplet combination of binimetinib, encorafenib and Erbitux (BINI 45 mg twice daily, ENCO 300 mg daily and CETUX per label). As of the data cutoff date of August 9, 2017, 30 patients were treated in the safety lead-in and received the triplet combination. Out of the 30 patients, 29 had a BRAFV600E mutation. Microsatellite instability-high (MSI-H) was detected in only one patient. The triplet demonstrated good tolerability, supporting initiation of the randomized portion of the study. In addition, promising initial clinical activity was observed, with a confirmed overall response rate (ORR) of 41%, including a complete response, in patients with the BRAFV600E mutation, a group of patients with historically poor outcomes. Responses were observed in 10 out of 17 patients (59%) who had received only one prior line of therapy. Out of 28 patients with both a BRAFV600E mutation and a post-baseline assessment, 27 showed tumor regression.

In the safety lead-in, the triplet combination was generally well-tolerated. The most common grade 3 or 4 AEs observed in at least 10% of patients were nausea (10%), vomiting (10%), increased blood creatine kinase (10%) and urinary tract infection (10%). Three patients discontinued treatment due to AEs with only one considered related to treatment. At the time of the analysis, 76% of patients remain on study treatment after a median duration of treatment of 5.6 months (range 1.0 – 9.3 months).

“The BRAF mutation carries a very poor prognosis for patients with advanced colorectal cancer, and is particularly unresponsive after first-line therapy,” said Dr. Victor Sandor, Chief Medical Officer. “In the safety lead-in, the triplet combination was well tolerated and showed impressive results with a confirmed overall response rate of 41%. Several patients also showed prolonged stable disease, with 76% of patients overall continuing on therapy after a median duration of exposure of 5.6 months. These results are unprecedented for this patient population based on existing standards of care.”

BEACON CRC was initiated based on results from a Phase 2 study that included the combination of encorafenib and cetuximab in 50 patients with advanced BRAF-mutant CRC, and that was presented at the 2016 ASCO (Free ASCO Whitepaper) annual meeting. In this Phase 2 study, Overall Survival for patients treated with the doublet combination of encorafenib and cetuximab exceeded one year, which is more than double several separate historical standard of care published benchmarks for this population. [12-17] In addition, confirmed ORR from this study was 22%, whereas historical published benchmarks in this patient population using standard of care regimens range between 4-8%. [15-18]

Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Of these, nearly 750,000 were diagnosed in men, and 614,000 in women. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer. In the U.S. alone, an estimated 135,430 patients will be diagnosed with cancer of the colon or rectum in 2017, and approximately 50,000 are estimated to die of their disease. [5] In the United States, BRAF mutations are estimated to occur in 10 to 15 percent of patients with colorectal cancer and represent a poor prognosis for these patients.[6-9] Based on recent estimates, the prevalence of MSI-H in tumors from patients with metastatic BRAF-mutant CRC ranged from 14% in a Phase 1b/2 trial (NCT01719380) (Array, data on file) to 18% from a recent Southwestern Oncology Group (SWOG) randomized phase 2 study.[10]

NEW CLINICAL TRIAL INITIATED IN MICROSATELLITE STABLE METASTATIC CRC (MSS CRC) WITH BRISTOL-MYERS SQUIBB; TRIAL WITH MERCK EXPECTED TO BEGIN IN SECOND HALF OF 2017
Array is collaborating separately with Bristol-Myers Squibb and Merck to study binimetinib plus anti-PD-1 therapy in patients with MSS CRC. The majority of metastatic colorectal cancers exhibit an MSS phenotype. [11]

The clinical trial in collaboration with Bristol-Myers Squibb, which was initiated in September 2017, will investigate the safety, tolerability and efficacy of binimetinib in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) and Opdivo + Yervoy (ipilimumab) regimen in patients with advanced MSS CRC and presence of a RAS mutation who have received one or two prior lines of therapy. The trial in collaboration with Merck, which is expected to begin during the second half of 2017, will investigate the safety, tolerability and efficacy of binimetinib with Merck’s KEYTRUDA (pembrolizumab) as part of multiple novel regimens. Array entered into these collaborations based on the growing body of preclinical and clinical evidence that the immune activity of an anti-PD-1 therapy can be enhanced when combined with a MEK inhibitor, such as binimetinib.

The Phase 1/2 studies are expected to establish recommended dose regimens and explore the preliminary anti-tumor activity of the combinations. Results from these studies will be used to determine optimal approaches to further clinical development of these combinations. Under the Merck agreement, Merck will act as the sponsor of this clinical trial, and Array will supply Merck with binimetinib for use in the trial. Under the Bristol-Myers Squibb agreement, Array and Bristol-Myers Squibb will jointly support the study with Array acting as the sponsor.

OTHER CLINICAL UPDATES: ARRY-382 and ARRY-797 programs
Array is advancing a Phase 1/2 dose escalation trial of ARRY-382 in combination with pembrolizumab (Keytruda), a PD-1 antibody, in patients with advanced solid tumors, including melanoma and non-small cell lung cancer. ARRY-382 is a wholly-owned, highly selective and potent, small molecule inhibitor of CSF-1R kinase activity. A poster entitled “Phase 1b/2 dose-escalation study of ARRY-382, an oral inhibitor of colony-stimulating factor-1 receptor (CSF1R), in combination with pembrolizumab for treatment of patients with advanced solid tumors” will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting on November 10, 2017. The presentation will provide preliminary safety and pharmacokinetic data as well as initial efficacy data in patients with advanced solid tumors.

Array plans to initiate a Phase 3 trial of ARRY-797, an oral, selective p38 MAPK inhibitor, in patients with LMNA A/C-related dilated cardiomyopathy as it evaluates options regarding the asset, including advancing it internally, partnering the program or creating a separate company to advance development and commercialization. LMNA A/C-related dilated cardiomyopathy is a rare, degenerative cardiovascular disease caused by mutations in the LMNA gene and characterized by poor prognosis.

FINANCIAL HIGHLIGHTS
Novartis Financial Commitment
Novartis continues to substantially fund all ongoing trials with binimetinib and encorafenib that were active or planned as of the close of the Novartis Agreements in 2015, including the COLUMBUS Phase 3 trial. Reimbursement revenue from Novartis was approximately $94.1 million for the 12 months ended September 30, 2017, of which $18.2 million was recorded in the quarter ended September 30, 2017. Total revenue and upfront payment collected from Novartis since the start of the 2015 agreement is $326.3 million.

Raised $258.8 million in public offering
Array completed an underwritten public offering of 24.1 million shares of its common stock at a price of $10.75 per share on September 19, 2017. The total gross proceeds from the offering were $258.8 million, before underwriting discounts, commissions and offering expenses.

First Quarter of Fiscal 2018 Compared to Fourth Quarter of Fiscal 2017 (Sequential Quarters Comparison)

Revenue for the first quarter of fiscal 2018 was $29.7 million, compared to $33.8 million for the prior quarter due to slightly higher milestones received in the prior quarter.
Cost of partnered programs for the first quarter of fiscal 2018 was $11.8 million, compared to $10.1 million for the prior quarter. The increase was primarily due to higher costs incurred for the BEACON CRC trial as it continues to advance.
Research and development expense was $41.4 million, compared to $39.1 million in the prior quarter. The increase was driven by $6.4 million in one-time charges for commercial drug supply of binimetinib and encorafenib from Novartis, which was partially offset by reduced expenses associated with the Novartis transitioned studies.
Loss from Operations for the quarter was $35.5 million, which includes $6.2 million of stock-based compensation and depreciation expense. The higher than normal stock-based compensation expense was primarily due to an employee departure. This compares to a loss from operations of $26.3 million in the previous quarter, which included $3.7 million of stock-based compensation and depreciation expense. The increase in net loss was primarily due to non-recurring costs for commercial drug supply from Novartis, increased stock-based compensation expense and decrease in reimbursement revenue from Novartis.
Net loss for the first quarter was $38.0 million, or ($0.22) per share, compared to $29.6 million, or ($0.17) per share, in the prior quarter.
Cash, Cash Equivalents and Marketable Securities as of September 30, 2017 were $464.3 million.
First Quarter of Fiscal 2018 Compared to First Quarter of Fiscal 2017 (Prior Year Comparison)

Revenue for the first quarter of fiscal 2018 decreased $9.5 million compared to the same quarter of fiscal 2017. The decrease was primarily due to decreased reimbursement revenue for the Novartis transitioned studies.
Cost of partnered programs increased $2.9 million compared to the first quarter of fiscal 2017. The increase was primarily due to higher costs incurred for the BEACON CRC trial.
Research and development expense decreased $5.1 million, compared to the first quarter of fiscal 2017. The decrease was due to expenses associated with the Novartis transitioned studies.
Net loss for the first quarter of fiscal 2018 was $38.0 million, or ($0.22) per share, compared to $28.6 million, or ($0.20) per share, for the same quarter in fiscal 2017. The increase in net loss was primarily due to a decrease in reimbursement revenue from Novartis and non-recurring costs for commercial drug supply from Novartis.
CONFERENCE CALL INFORMATION
Array will hold a conference call on Tuesday, October 31, 2017 at 9:00 a.m. Eastern Time to discuss these results and provide an update on the progress of its key clinical development programs. Ron Squarer, Chief Executive Officer, will lead the call.

Date:
Tuesday, October 31, 2017
Time:
9:00 a.m. Eastern Time
Toll-Free:
(844) 464-3927
Toll:
(765) 507-2598
Pass Code:
94698561
Webcast, including Replay and Conference Call Slides:
View Source

About Array BioPharma
Array BioPharma Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule drugs to treat patients afflicted with cancer. Nine registration studies are currently advancing related to seven Array-owned or partnered drugs: binimetinib (MEK162), encorafenib (LGX818), selumetinib (partnered with AstraZeneca), danoprevir (partnered with Roche), ipatasertib (partnered with Genentech), larotrectinib (partnered with Loxo Oncology) and tucatinib (partnered with Cascadian Therapeutics).

References
[1] Melanoma Skin Cancer. American Cancer Society. Available at: View Source (link is external). Accessed June 2017.
[2] A Snapshot of Melanoma. National Cancer Institute. Available at: View Source (link is external). Accessed June 2017.
[3] Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. View Source (link is external). Accessed June 2017.
[4] Klein O, et al. (2013) BRAF inhibitor activity in V600R metastatic melanoma. Eur J Cancer. 49(5):1073-1079.
[5] Cancer Facts & Figures 2017. American Cancer Society. Available at: View Source (link is external). Accessed July 2017.
[6] Saridaki Z, et al. (2013) BRAFV600E Mutation Analysis in Patients with Metastatic Colorectal Cancer (mCRC) in Daily Clinical Practice: Correlations with Clinical Characteristics, and Its Impact on Patients’ Outcome. PLoS ONE 8(12): e84604. doi:10.1371/journal.pone.0084604
[7] Sorbye H, et al. (2015) High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort. PLoS ONE 10(6): e0131046. doi:10.1371/journal.pone.0131046
[8] Loupakis F, et al. (2009) KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. British Journal of Cancer 101(4), 715 – 721
[9] Vecchione, et al. (2016) A Vulnerability of a Subset of Colon Cancers with Potential Clinical Utility. Cell 165, 317–330
[10] Kopetz et al. J Clin Oncol. 2017;35:520-20
[11] Boland, C. Richard, et al. (2010) Microsatellite Instability in Colorectal Cancer. Gastroenterology, 138(6): 2073–2087.e3. doi:10.1053/j.gastro.2009.12.064
[12] Ulivi et al., J Transl Med. 2012
[13] Saridaki et al., PLoS One. 2013
[14] Loupakis et al., Br J Cancer. 2009
[15] De Roock et al., Lancet Oncol, 2010
[16] Peeters et al., ASCO (Free ASCO Whitepaper) 2014
[17] Kopetz et al., ASCO (Free ASCO Whitepaper) 2017
[18] Seymour et al., Lancet Oncol, 2013 (supplementary appendix)

Forward-Looking Statement
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements about the timing of the announcement of the results of clinical trials for our proprietary and our partnered programs, the timing of the completion or initiation of further development of our wholly-owned and our partnered programs, including the timing of regulatory filings or approvals, expectations that events will occur that will result in greater value for Array, the potential for the results of ongoing preclinical and clinical trials to support regulatory approval or the marketing success of a drug candidate, our ability to partner our proprietary drug candidates for up-front fees, milestone and/or royalty payments, our future plans to progress and develop our proprietary programs, our future capital requirements and the plans of our collaborators to progress and develop programs we have licensed to them, and our plans to build a commercial-stage biopharmaceutical company. These statements involve significant risks and uncertainties, including those discussed in our most recent annual report filed on Form 10-K, in our quarterly reports filed on Form 10-Q, and in other reports filed by Array with the Securities and Exchange Commission. Because these statements reflect our current expectations concerning future events, our actual results could differ materially from those anticipated in these forward-looking statements as a result of many factors. These factors include, but are not limited to, our ability to continue to fund and successfully progress internal research and development efforts and to create effective, commercially-viable drugs; risks relating to the regulatory approval process for our drug candidates, which may not result in approval for our drug candidates, cause delays in development or require that we expend more resources to obtain approval than expected; risks associated with our dependence on our collaborators for the clinical development and commercialization of our out-licensed drug candidates; the ability of our collaborators and of Array to meet objectives tied to milestones and royalties; our ability to effectively and timely conduct clinical trials in light of increasing costs and difficulties in locating appropriate trial sites and in enrolling patients who meet the criteria for certain clinical trials; risks associated with our dependence on third-party service providers to successfully conduct clinical trials within and outside the United States; our ability to achieve and maintain profitability and maintain sufficient cash resources; the extent to which the pharmaceutical and biotechnology industries are willing to in-license drug candidates for their product pipelines and to collaborate with and fund third parties on their drug discovery activities; our ability to out-license our proprietary candidates on favorable terms; and our ability to attract and retain experienced scientists and management. We are providing this information as of October 31, 2017. We undertake no duty to update any forward-looking statements to reflect the occurrence of events or circumstances after the date of such statements or of anticipated or unanticipated events that alter any assumptions underlying such statements.

-more-



Array BioPharma Inc.
Condensed Statements of Operations
(Unaudited)
(in thousands, except per share amounts)















Three Months Ended






September 30,






2017

2016
Revenue






Reimbursement revenue


$ 18,192

$ 31,321

Collaboration and other revenue


8,008

6,289

License and milestone revenue


3,546

1,661


Total revenue


29,746

39,271









Operating expenses






Cost of partnered programs


11,759

8,845

Research and development for proprietary programs


41,445

46,563

General and administrative


12,048

7,862


Total operating expenses


65,252

63,270









Loss from operations


(35,506)

(23,999)









Other income (expense)






Impairment loss related to cost method investment


—

(1,500)

Realized gains on investments and other


—

—

Change in fair value of notes payable


200

(200)

Interest income


525

70

Interest expense


(3,213)

(2,979)


Total other expense, net


(2,488)

(4,609)









Net loss


$ (37,994)

$ (28,608)


















Net loss per share – basic


$ (0.22)

$ (0.20)
Net loss per share – diluted


$ (0.22)

$ (0.20)









Weighted average shares outstanding – basic


174,772

145,100
Weighted average shares outstanding – diluted


174,772

145,100


















Summary Balance Sheet Data
(Unaudited)
(in thousands)






September 30, 2017

June 30, 2017












Cash, cash equivalents and marketable securities


$ 464,336

$ 235,055



Working capital


$ 402,899

$ 200,626



Total assets


$ 502,309

$ 279,145



Long-term debt, net


$ 123,266

$ 121,305



Total stockholders’ equity


$ 226,621

$ 11,727


CONTACT:
Tricia Haugeto

(303) 386-1193

[email protected]


View original content with multimedia:View Source

SOURCE Array BioPharma Inc.

On October 31, 2017 Novartis reported that the company has submitted a supplemental Biologics License Application (sBLA) to the US Food and Drug Administration (FDA) for KymriahTM (tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant (ASCT) (Press release, Novartis, OCT 31, 2017, View Source [SID1234521328]). In April 2017, Novartis received Breakthrough Therapy designation for r/r DLBCL which, if approved, would be the second indication for Kymriah. In August 2017, Kymriah became the first available chimeric antigen receptor T cell (CAR-T) therapy when it received FDA approval five weeks prior to its PDUFA date and was launched for patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or has relapsed at least twice. Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient’s own T cells to fight cancer.

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!

“Kymriah represents a historic breakthrough in the evolution of individualized immunotherapy and we are committed to bringing this innovation to as many patients who may benefit as possible,” said Vas Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis. “The response rates we’ve seen in the JULIET trial show that Kymriah has the potential to transform treatment for these patients and we look forward to collaborating with the FDA to make it available to patients for this second indication.”

DLBCL is the most common form of non-Hodgkin lymphoma (NHL), a cancer of the lymphatic system, accounting for up to 40% of all NHL cases globally[1]. Roughly 50-60% of patients with DLBCL achieve and maintain complete remission after first-line therapy; however, roughly one-third of patients relapse after receiving first-line treatment[2],[3]. Only about 25% of patients with r/r DLBCL are eligible for ASCT, the mainstay of secondary treatment. If left untreated, r/r DLBCL has a life expectancy of three to four months[2].

“The approval of tisagenlecleucel in the treatment of children and young adults with second relapse or refractory B-cell ALL was a watershed moment in the journey for researchers to develop immunocellular therapies,” said Stephen Schuster, MD, director of the Lymphoma Program and Lymphoma Translational Research, University of Pennsylvania Perelman School of Medicine. “The data show this therapy could change the treatment paradigm for patients with r/r DLBCL as we’ve seen durable complete responses in patients who previously relapsed or were refractory to prior therapies, and this second filing is a significant step toward realizing its potential for even more patients who are currently battling fatal blood cancers.”

Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

The submission is based on results from the Novartis-sponsored, global, multi-center Phase II JULIET study (NCT02445248), the first global, multi-center registration study for Kymriah in adult patients with r/r DLBCL. JULIET was conducted in collaboration with Penn and is the largest study examining a CAR-T therapy exclusively in DLBCL, enrolling patients from 27 sites in 10 countries across the US, Canada, Europe, Australia and Japan. Data from the six-month primary analysis of JULIET will be presented at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2017.

Novartis plans to submit an additional application for marketing authorization for Kymriah with the European Medicines Agency (EMA) in both DLBCL and pediatric ALL later this year. Novartis plans additional regulatory filings for Kymriah outside the US and EU in 2018.

About CAR-T
CAR-T is different from typical small molecule or biologic therapies because it is manufactured for each individual patient using their own cells. During the treatment process, T cells are drawn from a patient’s blood and reprogrammed in the laboratory to create T cells that are genetically coded to hunt the patient’s cancer cells and other B cells expressing a particular antigen.

About Kymriah Manufacturing
Kymriah is manufactured for each individual patient using their own cells at the Novartis Morris Plains, New Jersey facility. Novartis has successfully demonstrated a 22-day turnaround time for manufacturing Kymriah in the commercial setting, and this will continue to be the target. The reliable and integrated manufacturing and supply chain platform for Kymriah allows for an individualized treatment approach on a global scale. The process includes cryopreservation of a patient’s harvested (or leukapheresed) cells, giving treating physicians and centers the flexibility to initiate therapy with Kymriah based on the individual patient’s condition.

Building on the company’s experience, having manufactured CAR-T cells for over 250 patients from 11 countries across various indications in clinical trials, it has demonstrated a high-quality and reproducible product. Novartis continues to advance its CAR-T manufacturing expertise and make investments to support the anticipated demand to meet the needs of patients.

Novartis Leadership in Immuno-Oncology
Novartis is at the forefront of investigational immunocellular therapy as the first pharmaceutical company to initiate global CAR-T trials, and has significantly invested in CAR-T research and worked with pioneers in the field. Active research programs are underway targeting other hematologic malignancies and solid tumors, and include efforts focused on next generation CAR-Ts that involve simplified manufacturing schemes and gene edited cells.

KymriahTM (tisagenlecleucel) Important Safety information (for pediatric and young adult patients with B-cell precursor acute lymphoblastic leukemia)
The full prescribing information, including Boxed WARNING, for Kymriah can be found at:
View Source (link is external)

Kymriah may cause side effects that are severe or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including high fever, difficulty breathing, chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.

Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their health care provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.

Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) in the US called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion.
Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their health care provider right away if they develop fever, chills, or any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient’s health care provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their health care provider right away if they get a fever, are feeling tired, or have bruising or bleeding.

Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their health care provider about their treatment with Kymriah before receiving a live virus vaccine.

After treatment with Kymriah, patients will be monitored life-long by their health care provider, as they may develop secondary cancers or recurrence of their leukemia.

Patients should not drive, operate heavy machinery, or do other dangerous activities for 8 weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness, and seizures.

Some of the most common side effects of Kymriah are difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, and dizziness/lightheadedness. However, these are not all of the possible side effects of Kymriah. Patients should talk to their health care provider for medical advice about side effects.

Prior to a female patient starting treatment with Kymriah, their health care provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. If either sex partner has received Kymriah, patients should talk to their health care provider about birth control and pregnancy.

Patients should tell their health care provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, regarding our ability to implement, scale and sustain commercial manufacturing for the investigational or approved products described in this press release, regarding our ability to build and sustain a network of treatment centers to offer the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that Novartis will successfully implement, scale and sustain commercial manufacturing for the investigational or approved products described in this press release, or successfully build and sustain a network of treatment centers to offer the investigational or approved products described in this press release. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, our ability to successfully implement, scale and sustain commercial manufacturing and build and sustain a network of treatment centers; the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; general economic and industry conditions, including the effects of the persistently weak economic and financial environment in many countries; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.