1stOncology™: Cancer Intelligence Service – Page 13873 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

NewLink Genetics Reports First Quarter 2019 Financial Results and Provides Clinical Activities Update

On May 8, 2019 NewLink Genetics Corporation (NASDAQ:NLNK) reported financial results for the first quarter ended March 31, 2019 and provided an update on clinical activities (Press release, NewLink Genetics, MAY 8, 2019, View Source [SID1234535919]).

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 continued to make progress across our clinical programs this year. We look forward to presenting additional encouraging data later this month on NLG802. We were also pleased to present Phase 2 results for NLG207 in combination with weekly paclitaxel for patients with recurrent ovarian cancer at AACR (Free AACR Whitepaper), which demonstrated an encouraging safety profile supporting the potential of NLG207 as a best-in-class topoisomerase 1 inhibitor for those women who had received multiple lines of therapy," said Charles J. Link, Jr, MD, Chairman and Chief Executive Officer of NewLink Genetics. "With a strong cash position of $113.2 million at the end of the quarter, we are well positioned to continue moving our clinical programs forward, and we anticipate sharing additional data from our pipeline in the coming quarters as we prioritize clinical development programs with a focus on indications with high unmet need and a potential path forward to registration."

Clinical Update and Anticipated Upcoming Milestones

The Company has had an abstract accepted, and plans to present updated data from a Phase 1 dose-escalation study of NLG802, a prodrug of indoximod, at the Immuno-Oncology 2019 2nd World Congress in Barcelona, Spain, May 23-24, 2019.

The Phase 2 study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel for patients with recurrent ovarian cancer, conducted in conjunction with The GOG Foundation, is complete. The Company recently presented results from this study at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, and we are evaluating NLG207 as a potential therapeutic in gynecologic malignancies.

Updated results from the cohort of patients with DIPG in the efficacy portion of a Phase 1b study of indoximod for the treatment of pediatric patients with recurrent malignant brain tumors are anticipated later in 2019.

In reference to NewLink Genetics’ partnered Ebola vaccine candidate, Merck recently announced that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application for this vaccine, V920 (rVSV∆G-ZEBOV-GP). In addition, completion of the rolling Biologics License Application (BLA) filing with the FDA by Merck is anticipated in 2019. Should this vaccine be approved by the FDA, a Priority Review Voucher (PRV) would be issued, in which NewLink Genetics owns a substantial financial interest.

Financial Results for the Three-Month Period Ended March 31, 2019

Cash Position: NewLink Genetics ended the quarter on March 31, 2019, with cash and cash equivalents totaling $113.2 million compared to $120.7 millionDecember 31, 2018. The Company projects its cash position is sufficient to fund planned operations through the end of 2021.

R&D Expenses: Research and development expenses for the first quarter of 2019 were $5.2 million, a decrease of $15.1 million from $20.3 million for the same period in 2018. The decrease was primarily due to reductions of $9.9 million in contract research and manufacturing spend, $2.2 million in personnel-related and stock compensation expense, $2.1 million in clinical trial expense, $500,000 in supplies and licensing, and $400,000 in legal and consulting expense.

G&A Expenses: General and administrative expenses in the first quarter of 2019 were $5.6 million, a decrease of $2.7 million from $8.3 million for the same period in 2018. The decrease was due primarily to reductions of $2.1 million in personnel-related and stock compensation expense, $605,000 in legal and consulting expense, offset by an increase of $72,000 in supplies and travel expense.

Net Loss: NewLink Genetics reported a net loss of $10.0 million or ($0.27) per diluted share for the first quarter of 2019 compared to a net loss of $18.3 million or ($0.49) per diluted share for the first quarter of 2018.

NewLink Genetics ended Q1 2019 with 37,276,102 shares outstanding.

Conference Call and Webcast Details

The Company has scheduled a conference call and webcast for 4:30 p.m. ET today to discuss its financial results and to give an update on clinical and business development activities. There will also be a question and answer session following management’s prepared remarks.

Access to the live conference call is available five minutes prior to the start of the call by dialing (855) 469-0612 (U.S.) or (484) 756-4268 (international) and using the conference ID 8457627. The conference call will be webcast live and a link to the webcast can be accessed through the NewLink Genetics website at www.NewLinkGenetics.com in the "Investors & Media" section under "Events and Presentations" or by clicking here. To ensure a timely connection, it is recommended that users register at least 10 minutes prior to the scheduled webcast. A replay of the call will be available approximately two hours after the completion of the call and can be accessed by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and using the conference ID 8457627. The replay will be available for two weeks from the date of the call.

About Indoximod

Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is a key immuno-oncology target, suppressing immune response and allowing for immune escape by degrading tryptophan with the resultant production of kynurenine. Indoximod reverses the immunosuppressive effects of low tryptophan and high kynurenine through mechanisms that include modulation of the AhR-driven transcription of genes that control immune function. This results in increased proliferation of effector T cells, increased differentiation into helper T cells rather than regulatory T cells, and downregulation of IDO expression in dendritic cells. Indoximod is being evaluated in combination with treatment regimens including chemotherapy, radiation, checkpoint blockade and cancer vaccines across multiple indications including DIPG, recurrent pediatric brain tumors, and AML.

About NLG802

NLG802 is an investigational, orally available prodrug of indoximod, a small molecule targeting the IDO Pathway. The IDO Pathway is one of the key immuno-oncology targets involved in regulating the tumor microenvironment and immune escape. NewLink Genetics is currently evaluating NLG802 in a Phase 1 dose-escalation clinical trial in cancer patients to assess the safety and pharmacokinetics of NLG802.

About NLG207

NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) consisting of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase 1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside cancer cells augments antitumor activity while reducing toxicity. Topoisomerase 1 inhibitors are a class of drugs that modify DNA damage responses in cancer cells. NewLink Genetics is evaluating NLG207 in a series of clinical trials in advanced refractory ovarian cancer patients.

Exicure, Inc. Reports First Quarter 2019 Financial Results and Reviews Corporate Progress

On May 8, 2019 Exicure, Inc. (OTCQB: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported financial results for the first quarter ended March 31, 2019 and provided an update on corporate progress (Press release, Exicure, MAY 8, 2019, View Source [SID1234535918]).

"Exicure continues to drive our SNA technology into the clinic and expand our therapeutic areas of interest. In the first quarter of 2019, we opened four clinical sites and began enrolling patients in the Phase 1b/2 trial of AST-008 for patients with advanced or metastatic solid tumors including, Merkel cell carcinoma, melanoma, squamous carcinoma and squamous cell carcinoma of the head and neck," said Dr. David Giljohann, Chief Executive Officer of Exicure. "We are also pursuing significant unmet medical need in rare dermatological indications through our partnership with Dermelix and are expanding our platform in neurology."

Corporate Progress

Launched Phase 1b/2 clinical trial of AST-008—AST-008 is an SNA consisting of toll-like receptor 9, or TLR9, agonists designed for immuno-oncology applications.

Received authorization from the FDA for a Phase 1b/2 clinical trial of AST-008

Opened four clinical sites and began dosing patients

Expects to release results of the Phase 1b stage of this trial late in 2019

Entered into partnership with Dermelix for rare dermatological conditions—Dermelix will initially develop a targeted therapy for the treatment of Netherton Syndrome (NS) and Exicure is currently screening sequences against the target genes.

Presented a scientific poster at ARVO 2019—This poster showed that in a rat eye model, our SNAs distributed to both the back and the front of the eye, persisted in the eye longer than did conventional oligonucleotides, and did not cause inflammation. These data support the therapeutic potential of SNAs for treating retinal and corneal eye diseases.

Presented a scientific poster at AAN 2019—This poster demonstrated that SNAs containing the same sequence as the approved SMA drug nusinersen, delivered by intrathecal injection to rats, widely distributed throughout the CNS and persisted to a greater extent than did nusinersen. These data support the therapeutic potential of SNAs for treating CNS disorders.

First Quarter 2019 Financial Results and Financial Guidance

Cash Position: As of March 31, 2019, Exicure had cash and cash equivalents of $22.2 million compared to $26.3 million as of December 31, 2018.

Research and Development (R&D) Expenses: Research and development expenses were $3.4 million for the quarter ended March 31, 2019, compared to $3.3 million for the quarter ended March 31, 2018.

The increase in research and development expense of $0.1 million was primarily due to higher platform and discovery-related expense of $0.2 million and higher employee related expenses of $0.2 million, mostly offset by lower clinical development programs expense of $0.3 million.

General and Administrative (G&A) Expenses: General and administrative expenses were $2.2 million for the quarter ended March 31, 2019, compared to $2.0 million for the quarter ended March 31, 2018. The increase in general and administrative expenses of $0.2 million was primarily due higher compensation and travel expenses, partially offset by lower legal fees.

Net Loss: Net loss was $5.3 million for the quarter ended March 31, 2019, compared to net loss of $5.5 million for the quarter ended March 31, 2018. The $0.2 million reduction in net loss is due to the $0.5 million in other income attributable to the (non-cash) fair value adjustment of our common stock warrant liability, partially offset by the increase in operating expenses of $0.3 million as described above.

Cash Runway Guidance: Exicure believes that, based on its current operating plans and estimates of expenses, as of the date of this press release, its existing cash and cash equivalents as of March 31, 2019, will be sufficient to meet its anticipated cash requirements into early 2020.

Jounce Therapeutics Reports First Quarter 2019 Financial Results

On May 8, 2019 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers for patient enrichment, reported financial results and provided a corporate update for the first quarter ended March 31, 2019 (Press release, Jounce Therapeutics, MAY 8, 2019, View Source [SID1234535905]).

"We have made significant progress in recent months by applying our Translational Science Platform and reverse translational approach to advance both our ongoing clinical and preclinical programs. Most importantly, at AACR (Free AACR Whitepaper), we presented promising new progression free and overall survival data from the ICONIC trial for patients stratified by our vopratelimab pharmacodynamic biomarker, ICOS hi CD4 T cells in the blood. Additionally, we presented validating preclinical data from our lead tumor-associated macrophage program, JTX-8064," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "With these key accomplishments in hand, we look forward to advancing our broader pipeline with the goal of three immunotherapies in the clinic in 2019. We remain focused on the underlying mechanistic science of our immunotherapies and understanding of the characteristics of responding patients in our mission to bring meaningful and long-lasting benefit to cancer patients with unmet needs."

Pipeline Highlights:
Vopratelimab (JTX-2011)

Key data presented at AACR (Free AACR Whitepaper) 2019: In April 2019, Jounce presented two posters on vopratelimab at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. Highlights from the poster presentations include:

Patients in the ICONIC trial with the emergence of ICOS hi CD4 T cells demonstrated improved progression free survival (PFS) and overall survival (OS) compared to patients with ICOS lo CD4 T cells, based on an analysis of a subgroup of patients with multiple solid tumor types including PD-1 inhibitor naive and PD-1 inhibitor experienced patients.

The characteristics of ICOS hi CD4 T cells associated with vopratelimab treatment via translational analyses demonstrated that vopratelimab stimulates only primed CD4 T cells with high levels of ICOS. The translational data shows that vopratelimab, unlike PD-1 inhibitors, leads to expansion and activation of peripheral CD4 T effector cells, and that these are observed in patients with clinical benefit.

On track for planned initiation of Phase 2 clinical studies: Based on the recently-presented AACR (Free AACR Whitepaper) data, Jounce plans to initiate additional Phase 2 clinical studies focusing on settings in which ICOS hi CD4 T effector cells exist or emerge and are primed to respond to vopratelimab, potentially leading to clinical benefit. The first of these studies will be a clinical trial of

jouncelogosmaller.jpg

vopratelimab in combination with ipilimumab in PD-1 inhibitor experienced patients in two tumor types, non-small cell lung cancer and bladder cancer. Additionally, Jounce expects to initiate a clinical trial of vopratelimab in combination with ipilimumab in PD-1 inhibitor naive patients with bladder cancer and a separate predictive biomarker study. Jounce expects to report preliminary efficacy data in 2020.

JTX-4014

On track to complete enrollment of Phase 1 study: Jounce remains on track to assess safety and select the recommended Phase 2 dose for JTX-4014, its PD-1 inhibitor, in 2019.

JTX-8064

New validating preclinical data presented at AACR (Free AACR Whitepaper) 2019: In April 2019, Jounce presented new preclinical data demonstrating the properties of JTX-8064, Jounce’s lead tumor associated macrophage candidate. JTX-8064 is an inhibitor of LILRB2 (leukocyte immunoglobulin like receptor B2; ILT4) and is believed to reprogram tumor-associated macrophages within the tumor microenvironment. Highlights from the poster presentation include:

When LILRB2 binds to its ligands, it maintains macrophages in the M2 or immuno-suppressive state.

When JTX-8064 blocks ligand binding to LILRB2, it induces an immune activating state in macrophages that may lead to the enhancement of the anti-tumor immune response.

Inhibiting LILRB2 induces pro-inflammatory cytokine secretion and a unique transcriptional profile suggestive of an M1-like shift in human macrophages to an immune stimulatory state.

On track to file IND and initiate Phase 1 clinical trial: Jounce expects to file an investigational new drug (IND) application and initiate a Phase 1 clinical trial of JTX-8064 in 2019.

First Quarter 2019 Financial Results:

Cash Position: As of March 31, 2019, cash, cash equivalents and investments were $173.2 million, compared to $195.9 million as of December 31, 2018. The decrease in cash, cash equivalents and investments was primarily due to operating costs incurred during the period.

Collaboration Revenue: Collaboration revenue was $11.0 million for the first quarter of 2019, compared to $11.2 million for the same period in 2018. Collaboration revenue represents non-cash revenue recognition relating to the $225.0 million upfront payment received in July 2016 upon the execution of Jounce’s global strategic collaboration with Celgene.

Research and Development Expenses: Research and development (R&D) expenses were $17.3 million for the first quarter of 2019, compared to $18.2 million for the same period in 2018. The decrease in R&D expenses was primarily due to $1.5 million of decreased external research and development costs attributable to JTX-4014 IND-enabling expenses incurred during the first quarter of 2018, partially offset by $0.5 million of increased employee compensation costs.

General and Administrative Expenses: General and administrative (G&A) expenses were $7.2 million for the first quarter of 2019, compared to $6.8 million for the same period in 2018. The increase in G&A expenses was primarily due to $0.7 million of increased employee compensation costs, including $0.3 million of increased stock-based compensation expense.

jouncelogosmaller.jpg

Net Loss: Net loss was $12.4 million for the first quarter of 2019, or a basic and diluted net loss per share of $0.38. Net loss was $13.0 million for the same period in 2018, or a basic and diluted net loss per share of $0.40. The decrease in net loss and net loss per share was primarily attributable to the decrease in operating expenses from the first quarter of 2018 to the first quarter of 2019.

Financial Guidance:
Jounce reiterates its expectation that cash burn on operating expenses and capital expenditures for the full year 2019 will be approximately $80.0 million to $95.0 million. Jounce expects to record approximately $50.0 million to $60.0 million in non-cash collaboration revenue in 2019 from the recognition of the Celgene upfront payment received in 2016.

Conference Call and Webcast Information:
Jounce Therapeutics will host a live conference call and webcast today at 8:00 a.m. ET. To access the conference call, please dial (866) 916-3380 (domestic) or (210) 874-7772 (international) and refer to conference ID 5789371. The live webcast can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days.

Cautionary Note Regarding Forward-Looking Statements:
Various statements in this release concerning Jounce’s future expectations, plans and prospects, including without limitation, Jounce’s expectations regarding operating expenses, capital expenditures, collaboration revenue and other financial results; the timing, progress and release of data for Phase 2 clinical studies of vopratelimab; the timing, progress and results of the Phase 1 trial of JTX-4014; the filing of an IND and initiation of a Phase 1 trial of JTX-8064 and the timing, progress and results of preclinical studies and clinical trials for Jounce’s product candidates and any future product candidates may constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "anticipate," "believe," "estimate," "expect," "intend," "may," "on track," "plan," "predict," "target," "potential" or similar terms, variations of such terms or the negative of those terms. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Jounce’s ability to successfully demonstrate the efficacy and safety of its product candidates and future product candidates; the preclinical and clinical results for its product candidates, which may not support further development and marketing approval; the potential advantages of Jounce’s product candidates; the development plans of its product candidates and any companion or complementary diagnostics; actions of regulatory agencies, which may affect the initiation, timing and progress of preclinical studies and clinical trials of Jounce’s product candidates; Jounce’s ability to obtain, maintain and protect its intellectual property; Jounce’s ability to manage operating expenses; Jounce’s ability to maintain its collaboration with Celgene and those risks more fully discussed in the section entitled "Risk Factors" in Jounce’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission as well as discussions of potential risks, uncertainties, and other

jouncelogosmaller.jpg

important factors in Jounce’s subsequent filings with the Securities and Exchange Commission. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Epigenomics AG Reports 2019 First Quarter Financial Results

On May 8, 2019 Epigenomics AG (FSE: ECX, OTCQX: EPGNY; the "Company") reported the financial results (according to IFRS; unaudited) for the first quarter of the FY 2019 (Press release, Epigenomics, MAY 8, 2019, View Source [SID1234535904]).

KEY HIGHLIGHTS

Financial

Total revenue increased to EUR 331 thousand (Q1 2018: EUR 309 thousand) primarily due to higher product revenue of EUR 322 thousand (Q1 2018: EUR 108 thousand), while licensing revenue decreased to EUR 9 thousand due to termination of licensing agreement for the Chinese market.
Other income in the first quarter of 2019 of EUR 499 thousand (Q1 2018: EUR 10 thousand) resulted primarily from exchange rate gains.
Selling and administrative expenses increased from EUR 1.8 million (Q1 2018) to EUR 2.4 million as a result of higher marketing expenses.
EBITDA (before share-based payment expenses) improved from EUR -3.2 million (Q1 2018) to EUR -3.0 million.
Net loss for the period improved to EUR -3.0 million (Q1 2018: EUR -3.2 million); loss per share reduced to EUR 0.08 (Q1 2018: EUR 0.13).
Cash consumption increased to EUR 4.3 million (Q1 2018: EUR 2.4 million) in the first quarter of 2019 due to higher operating cash outflows.
As of March 31, 2019, liquidity amounted to EUR 12.9 million (incl. marketable securities) compared to EUR 17.1 million at year-end 2018.

Operational highlights

On May 3, 2019, after the end of the reporting period, the Company announced that the Centers for Medicare & Medicaid Services (CMS) has accepted the Company’s application for a National Coverage Determination (NCD) review of Epi proColon, Epigenomics’ blood test for colorectal cancer screening. The NCD is one of two options to obtain CMS coverage for Epi proColon, which would represent a major U.S. market breakthrough for the Company.
Greg Hamilton, Chief Executive Officer of Epigenomics AG: "With the acceptance of our NCD application no decision has yet been made on coverage, but CMS has determined that there is a rationale to accept the NCD review at this time. The decision of the CMS is a major step to receive a positive coverage decision in 2019."

On January 7, 2019, the Company announced positive results from a microsimulation model for the Epi proColon blood test. Microsimulation models are utilized by various screening guideline groups in the U.S. to aid in the development of screening recommendations.
Reintroduction of the bi-partisan "Donald Payne Sr. Colorectal Cancer Detection Act" (HR 1765) to the U.S. House of Representatives at the end of March 2019 as a necessary step on the legislative path to reimbursement.

Outlook 2019

Revenue

The Company confirms revenue expectation in 2019 within the range of EUR 3.0 million to EUR 6.0 million even without Medicare coverage.

EBITDA /Cash consumption

On EBITDA before share-based payment expenses, Epigenomics expects to remain unchanged from the previous year’s guidance in a range of EUR -11.5 million to EUR -14.0 million. Based on the Company’s 2019 business plan, the cash consumption is expected to be in line with the EBITDA guidance (before share-based payment expenses).

Further information

The 2019 Q1 interim statement (unaudited) is available on the Epigenomics Website at: View Source

Conference call for analysts and investors

Epigenomics AG will host a conference call for analysts and investors today at 4.00 pm (CET) / 10.00 am (EDT). The webcast can be accessed on the company’s website: View Source

The dial-in numbers for the conference call are:

Dial-in number within Germany: +49 30 2325 31428
Dial-in number within the UK: +44 20 3872 0882
Dial-in number within the U.S.A.: +1 516 269 8974

Participants are kindly requested to dial in 10 minutes prior to the start of the call.

An audio replay of the conference call will be provided on Epigenomics’ website subsequently.

Daiichi Sankyo Announces [Fam-] Trastuzumab Deruxtecan Demonstrated Clinically Meaningful Response in Patients with Refractory HER2 Positive Metastatic Breast Cancer, a Population with High Unmet Need

On May 8, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca reported positive topline results for the pivotal phase 2 DESTINY-Breast01 trial of [fam-] trastuzumab deruxtecan (DS-8201) (Press release, Daiichi Sankyo, MAY 8, 2019, View Source [SID1234535903]). The HER2 targeting antibody drug conjugate (ADC) was evaluated in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1).

The response rate in DESTINY-Breast01, as assessed by an independent review committee, confirms in a heavily-pretreated global patient population the unprecedented clinical activity in the recently published phase 1 trial. The safety and tolerability profile of [fam-] trastuzumab deruxtecan was also consistent with previous experience. These results are expected to support planned global regulatory submissions, including the Biologics License Application with the U.S. Food and Drug Administration (FDA) anticipated in the first half of fiscal year 2019.

DESTINY-Breast01 is a pivotal phase 2, open-label, global, multicenter, two-part trial of [fam-] trastuzumab deruxtecan. The optimal dose of 5.4 mg/kg was previously identified in part one of the trial. Today’s results from part two evaluated the efficacy and safety of that dose in patients who have failed or discontinued previous treatment with T-DM1.

"These results confirm our commitment to pursue accelerated regulatory pathways in HER2 positive metastatic breast cancer with [fam-] trastuzumab deruxtecan," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "We are more dedicated than ever to our comprehensive and ambitious development strategy evaluating the potential across a spectrum of HER2expressing cancers including breast, gastric, lung and colorectal."

"We are encouraged to see positive data from [fam-] trastuzumab deruxtecan, with the DESTINY-Breast01 trial now reinforcing what earlier data have shown," said José Baselga, Executive Vice President and President R&D Oncology, AstraZeneca. "We believe this antibody drug conjugate has the potential to redefine the treatment of patients with HER2 expressing cancers, and we are eager to bring it as quickly as possible to patients with refractory HER2 positive breast cancer who continue to have high unmet medical need."

[Fam-] trastuzumab deruxtecan has been granted U.S. FDA Breakthrough Therapy Designation and Fast Track Designation for HER2 positive patients in the advanced or refractory breast cancer setting. A recent publication in The Lancet Oncology reported long-term phase 1 safety and preliminary efficacy results in HER2 positive metastatic breast cancer. This investigational agent is currently in development for the treatment of multiple HER2 expressing cancers, including in patients with HER2 low expression.

Daiichi Sankyo and AstraZeneca plan to present the data from DESTINY-Breast01 at an upcoming medical meeting.

About HER2

HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poorer prognosis in breast cancer patients.[1] To be considered HER2 positive, tumor cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH).IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+.1 A finding of IHC 3+ and/or FISH amplification is considered positive.1There are currently no targeted therapies for HER2 FISH negative, IHC 2+ or IHC 1+ tumors.

Unmet Need in HER2 Positive Breast Cancer

Approximately one in five breast cancers are HER2 positive.[2]Several unmet treatment needs remain today in HER2 positive metastatic breast cancer. Many HER2 positive breast cancers eventually advance to the point where no currently approved HER2 targeting medicine continues to control the disease;[3] after treatment with trastuzumab, pertuzumab, and T-DM1, optimal treatment is less clearly defined, and choices may be limited.[4]

About DESTINY-Breast01

DESTINY-Breast01 is a pivotal phase 2, open-label, global, multicenter, two-part trial evaluating the safety and efficacy of [fam-] trastuzumab deruxtecan in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with T-DM1. The primary endpoint of the trial is objective response rate. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival.

The first part of the trial includes a pharmacokinetic stage and a dose-finding stage to identify the recommended dose of [fam-] trastuzumab deruxtecan to be evaluated in the second part of the trial. The second part enrolled patients into one of two cohorts: patients resistant or refractory to T-DM1 (part 2a) and patients who discontinued treatment with T-DM1 for reasons other than resistant or refractory disease (part 2b). Enrollment into DESTINY-Breast01 was completed in September 2018 with 253 patients at more than 100 sites across North America, Europe, Japan and other countries in Asia.

The safety and tolerability profile of [fam-] trastuzumab deruxtecan in DESTINY-Breast01 was consistent with the recently published phase 1 trial, in which the most common adverse events (≥30 percent, any grade) included nausea, decreased appetite, vomiting, alopecia, fatigue, anemia, diarrhea, and constipation. Cases of drug-related pneumonitis, including grade 5 events, have also been reported in the clinical development program.

About [Fam-] Trastuzumab Deruxtecan

[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced program in AstraZeneca’s ADC Scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia, including five pivotal trials in HER2 expressing breast and gastric cancers, including in breast cancer patients with HER2 low expression. [Fam-] trastuzumab deruxtecan is also in phase 2 development for HER2 expressing advanced colorectal cancer and metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC, and phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancers.

[Fam-] trastuzumab deruxtecan was granted Breakthrough Therapy Designation in 2017 by the U.S. FDA for the treatment of patients with HER2 positive, locally-advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1. Fast Track Designation was also granted in the U.S. for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted medicines, including T-DM1. Trastuzumab deruxtecan has received SAKIGAKE designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare.

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication

in any country. Safety and efficacy have not been established.

About the Collaboration between Daiichi Sankyo and AstraZeneca

In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize [fam-] trastuzumab deruxtecan as a medicine worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: [fam-] trastuzumab deruxtecan, an antibody drug conjugate (ADC) for HER2 expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory FLT3-ITD acute myeloid leukemia (AML); and pexidartinib, an oral CSF1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com.