On March 3, 2020 Immunomic Therapeutics, Inc., a privately held clinical stage biotechnology company pioneering the study of nucleic acid immunotherapy platforms, reported that it successfully completed a pre-IND (Investigational New Drug) meeting with the U.S. Food and Drug Administration (FDA) regarding its First-In-Human (FIH) Phase I trial and development plans for ITI-1001 (Press release, Immunomic Therapeutics, MAR 3, 2020, View Source [SID1234555119]). The FDA addressed the Company’s questions and provided feedback on key components of the planned IND application for the candidate, ITI-1001, for the treatment of newly diagnosed Glioblastoma Multiforme (GBM).

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!

ITI-1001 is an investigational plasmid DNA vaccine therapy that leverages Immunomic’s proprietary UNITE platform to treat patients with newly diagnosed GBM. ITI-1001 is designed to target the pp65, IE-1, and gB viral antigens of Cytomegalovirus (CMV), expressed in GBM, but not in normal brain cells.

"We are pleased to have completed our pre-IND meeting with the FDA, which marks an important development milestone for Immunomic and the ITI-1001 program," said Dr. William Hearl, CEO of Immunomic Therapeutics. "We appreciate the guidance from the FDA as we move forward with our plans to initiate a Phase 1 trial for GBM in the US, which we hope will bring us closer to providing a therapeutic option to patients with this devastating disease."

In the planned First-In-Human (FIH) Phase I trial, Immunomic will evaluate the safety, tolerability, immunogenicity and preliminary efficacy of ITI-1001 in patients with Newly-Diagnosed Glioblastoma (GBM) Having Unmethylated MGMT Promoter Mutations. The Phase 1 trial is anticipated to start in 2021.

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein, an endogenous protein in humans, for immune processing. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach could put UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in Phase II clinical trials as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.

On March 3, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM), a commercial-stage biopharmaceutical company with eight oncology drug candidates in development around the world and a deep commercial presence in China, reported its audited financial results for the year ended December 31, 2019 and provides updates on key clinical and commercial developments (Press release, Hutchison China MediTech, MAR 3, 2020, View Source [SID1234555118]).

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!

"2019 was a year in which we laid the foundations for a new era for Chi-Med," said Simon To, Chairman of Chi-Med. "Our first launched drug, Elunate, is set to broaden patient access this year due to its recent addition to the NRDL1 in China. We are scaling up our oncology commercial team in preparation for the potential launch of surufatinib, our first un-partnered oncology drug candidate, late this year in non-pancreatic NET2; and another two NDA3 submissions are imminent, one with savolitinib in lung cancer and a second with surufatinib in pancreatic NET, with launches anticipated for 2021."

"Based on extensive clinical data, we also expect to initiate multiple global registration studies this year with fruquintinib, surufatinib and potentially savolitinib. China registration studies with certain of our hematological malignancy assets are also in planning."

"We believe that the potential launches of multiple new oncology products will address a broad range of unmet medical needs and benefit a large number of patients, propelling Chi-Med rapidly forward."

RECENT OPERATING HIGHLIGHTS

Set out below are some of Chi-Med’s operating highlights for 2019 and so far this year. For more details, please refer to "Operations Review" below.

SAVOLITINIB — GLOBAL

· AstraZeneca4 collaboration — Prime position in EGFR TKI5 resistant NSCLC6:

· EGFRm7 NSCLC patients with acquired resistance to Tagrisso driven by MET8 amplification: Published full results of TATTON study in The Lancet Oncology in 2020 for the savolitinib/Tagrisso combination reporting 30% ORR9 and 5.4 months’ median PFS10 in 69 patients;

The SAVANNAH Phase II study, with registration potential, underway in North and South America, Europe and Asia, is on-target for interim analysis in mid-2020 and enrollment completion by end-2020;

·EGFRm NSCLC patients with acquired resistance to Iressa or Tarceva driven by MET amplification: Published full results of TATTON study in Lancet Oncology for the savolitinib/Tagrisso combination reporting 64% ORR and 9.0 months’ median PFS in 93 patients; and

Completed enrollment in 70 patients Phase II registration study — MET Exon 14 deletion NSCLC: Interim China Phase II data presented at CSCO11. As a result of our regulatory interaction with the NMPA12, we now expect to submit savolitinib NDA in early 2020.

· Papillary renal cell carcinoma ("PRCC") — Renewed global development strategy:

· Actively evaluating restart in MET-driven PRCC: In late 2018, enrollment was terminated in SAVOIR, a global Phase III registration study of savolitinib monotherapy compared with sunitinib monotherapy in MET-positive PRCC. Data from the approximately 60 patients randomized in SAVOIR prior to termination has matured during 2019 and will be presented at an upcoming scientific conference in mid-2020. Based on these data, AstraZeneca and Chi-Med are actively evaluating the opportunity to restart clinical work in PRCC for monotherapy savolitinib; and

· Preliminary signal for savolitinib/Imfinzi (PD-L113) combination in all PRCC: Presented data for the PRCC cohort of the CALYPSO Phase II study at ASCO (Free ASCO Whitepaper) GU14 showing the combination was tolerable and associated with durable efficacy. Median OS15 was 12.3 months and twelve-month OS rate was 52%. Based on these data, AstraZeneca and Chi-Med continue to explore development of the savolitinib and Imfinzi combination.

·Promising savolitinib efficacy in MET-amplified gastric cancer: The VIKTORY Phase II umbrella trial results were published in Cancer Discovery16. VIKTORY sequenced 715 metastatic gastric cancer patients, with MET-amplification observed in 3.5% of patients. In MET-amplified gastric cancer patients, savolitinib monotherapy met pre-specified 6-week PFS rate and reported an ORR of 50%.

SURUFATINIB — CHINA

·First targeted therapy to address NETs of all origins: Recently reported two positive Phase III studies, SANET-ep (mid-2019) in non-pancreatic NET and SANET-p (early 2020) in pancreatic NET. Both studies were terminated early following positive interim analyses that confirmed they had already met their median PFS primary endpoint:

· China Non-pancreatic NET: Presented full results of SANET-ep Phase III study at ESMO (Free ESMO Whitepaper)17 reporting a median PFS for surufatinib of 9.2 months as compared to 3.8 months for placebo (HR 0.334, p<0.0001). An NDA for the treatment of non-pancreatic NETs was submitted to the NMPA in China in November 2019 and Priority Review status was granted in December 2019; and

· China Pancreatic NET: Following positive interim analysis and early termination of the SANET-p Phase III study, NDA preparations are now underway.

·Initiated China Phase II/III study in biliary tract cancer ("BTC"): Based on preliminary Phase Ib/IIa data, we initiated a Phase IIb/III registration study in BTC in China in March 2019; and

·Progressed PD-118 combination development: Completed a Phase I dose-finding study in China of surufatinib plus Tuoyi, an approved PD-1 monoclonal antibody from Junshi19, then initiated an exploratory Phase II study of the combination in early 2020 in multiple solid tumor indications. Phase I development of surufatinib plus Tyvyt, an approved PD-1 monoclonal antibody from Innovent20, is also in planning.

FRUQUINTINIB — CHINA

·Progress on Elunate (fruquintinib capsules) in third-line colorectal cancer ("CRC") in China:

· 17.6 million in sales during 2019: In-market sales of Elunate to third-parties, as provided by Lilly21, in the first full year since its late 2018 launch; and

·Inclusion in the National Reimbursement Drug List ("NRDL"): Elunate was included in the China NRDL in November 2019, with reimbursement effective January 1, 2020. NRDL inclusion now makes Elunate a highly attractive approved therapy in third-line CRC in China in terms of price, efficacy and safety profile. Elunate sales22 in January-February 2020, were $6.6 million.

· Phase III interim analysis in second-line gastric cancer: In April 2019, an interim analysis for futility of the FRUTIGA study in China was performed. The IDMC23 recommended to continue the study without changes; and

·Progressed PD-1 combination development: Approaching completion of Phase I dose-finding study in China of Elunate plus Tyvyt (Innovent). Phase I development of Elunate plus genolimzumab, a PD-1 monoclonal antibody under development by Genor24, is also now underway.

OTHER DEVELOPMENT CANDIDATES — CHINA

· Non-Hodgkin’s lymphoma ("NHL"): Advanced Phase Ib dose expansion of both of our NHL assets, HMPL-523 (selective Syk25 inhibitor) and HMPL-689 (selective PI3Kδ26 inhibitor) in China. We expect these Phase I/Ib studies to inform our China registration study decisions in 2020;

· HMPL-453 — selective FGFR27 1/2/3 inhibitor: We completed Phase I development, with a Phase II study in advanced malignant mesothelioma in China set to initiate; an

IND28 clearance in China for HMPL-306: Our ninth in-house discovered asset, an IDH29 1/2 dual inhibitor, received China IND clearance in late 2019 with Phase I set to initiate.

INTERNATIONAL OPERATIONS

· Global development footprint: Through our International organization, based in New Jersey, we have rapidly expanded our clinical and regulatory capabilities in the U.S., Europe and now Japan;

· Fruquintinib: Completed EOP230 meetings with U.S. Food and Drug Administration ("FDA") in February 2020, regarding our global Phase III, the FRESCO2 study, in colorectal cancer. Europe and Japan EOP2 meetings are planned shortly;

·Surufatinib: Data from a U.S. Phase I/Ib study were presented at ESMO (Free ESMO Whitepaper). In late 2019, the U.S. FDA granted Orphan Drug designation for the treatment of pancreatic NET. Regulatory consultations in U.S., Europe and Japan are underway, to clarify registration pathway for surufatinib in NETs; and

·HMPL-523 and HMPL-689: Expanded development into the U.S. and Europe during 2019. Twenty Phase I sites are now enrolling and have completed multiple dose cohorts.

ORGANIZATION

·Chi-Med Group compensation and share-based incentive policy: The Group has comprehensively reviewed its compensation and share-based incentives policies, performed benchmarking research on peer group U.S. and China biotech companies and established a new competitive policy to ensure we are able to attract and retain top talent; and

· Establishment of China oncology commercial organization: Currently over 140 commercial staff, aiming to recruit a total of 300-350 staff to support potential surufatinib launch in late 2020.

UPDATE ON IMPACT OF COVID-19

·Improvising amid Covid-19 challenges: The outbreak is posing some challenges to our operations resulting from restrictions on movement in China. Reduced patient hospital visits for clinical assessment affected the conduct of certain clinical studies and commercial team activities. To-date, none of our manufacturing operations in China have been materially affected. Our teams have adapted quickly and effectively thus far across our businesses, and we will continue to closely monitor what is an evolving situation. At this stage we are unable to assess the long-term effect of the outbreak, if any.

KEY EVENTS PLANNED FOR 2020

Early 2020:

· Savolitinib — Phase Ib/II data (CALYPSO) — PRCC cohort overall survival results for the Imfinzi / savolitinib combination presented at ASCO (Free ASCO Whitepaper) GU (February 2020);

· HMPL-453 — Phase II study start — FGFR 1/2/3 inhibitor in advanced malignant mesothelioma;

·Savolitinib — NDA submission in MET exon 14 deletion NSCLC in China — first NDA submission globally for savolitinib;

· Surufatinib — NDA submission in pancreatic NET in China — following the recent positive SANET-p Phase III interim analysis;

·PD-1 combos — Initiation of multiple Phase II studies in China — for surufatinib/fruquintinib in combination with Tuoyi/Tyvyt; and

· PD-1 combos — Phase I dose-finding data for surufatinib plus Tuoyi combination — presentation of preliminary data at major scientific conference.

Mid-2020:

HMPL-306 — First in Human dose of IDH 1/2 inhibitor — initiate Phase I study in China;

·Savolitinib — Data from terminated Phase III study (SAVOIR) — presentation at major scientific conference of data comparing savolitinib to sunitinib in MET-driven PRCC patients; Mature data from about 60 patients;

Savolitinib — Interim analysis on SAVANNAH — interim analysis on first ~50 patients on SAVANNAH Phase II study of the savolitinib/Tagrisso combination;

Surufatinib — Completion of global regulatory consultations — clarity on U.S., Europe and Japan registration pathway for surufatinib in NETs. Initiation of required clinical studies in U.S. and Europe;

Savolitinib — MET exon 14 deletion NSCLC data — presentation of full data from the savolitinib Phase II registration intent study at major scientific conference;

Surufatinib — Phase III data (SANET-p) — presentation of full data from the SANET-p study in pancreatic-NET patients at a major scientific conference;

Fruquintinib — Second Phase III interim analysis (FRUTIGA) — interim analysis for futility in second-line gastric cancer Phase III in China of fruquintinib / Taxol (paclitaxel) combination;

Fruquintinib — Global Phase III study (FRESCO2) — initiation of registration study of fruquintinib in >3rd line colorectal cancer in U.S., Europe and Japan; and

HMPL-523 — Global Phase Ib expansion — in indolent NHL in U.S. and Europe.

Late 2020:

Surufatinib — Phase II/III interim analysis — for futility in second-line BTC in China;

· Surufatinib — Potential NDA approval and launch for non-pancreatic NET in China — first un-partnered oncology drug launch for Chi-Med in China. Commercial team of 300-350 medical sales personnel in place for launch;

· HMPL-689 — Potential registration study start — in indolent NHL in China;

Fruquintinib — Enrollment completion of FRUTIGA — to complete enrollment of China Phase III registration study in second-line gastric cancer;

Savolitinib — Enrollment completion of SAVANNAH — AstraZeneca to complete enrollment of global Phase II study, with registration potential, of savolitinib/Tagrisso combination; and

HMPL-689 — Global Phase Ib expansion — in indolent NHL in U.S. and Europe.

FINANCIAL HIGHLIGHTS

The items below are selected financial data for the year ended December 31, 2019. All dollars are expressed in US dollar currency unless otherwise stated. For more details, please refer to "Financial Review", "Operations Review" and "Audited Consolidated Financial Statements" below.

OVERALL GROUP:

Group revenue of $204.9 million (2018: $214.1m).

Net loss attributable to Chi-Med of $106.0 million (2018: net loss of $74.8m).

Adjusted Group net cash flows excluding financing activities was -$82.3 million (2018: -$49.1m). Cash from our Commercial Platform, as well as cash received from our multi-national partners, continued to offset a material portion of our R&D31 expenses.

Recent Nasdaq follow-on strengthens cash position. We held cash, cash equivalents and short-term investments of $217.2 million as of December 31, 2019 (December 31, 2018: $301.0m). In January 2020, we conducted a Nasdaq follow-on offering, raising an additional $110.1 million in net proceeds, to further strengthen our cash position; and

Additional unutilized bank facilities of $119.3 million (December 31, 2018: $119.3m) and borrowings of $26.8 million (December 31, 2018: $26.7m).

INNOVATION PLATFORM:

Consolidated revenue was $16.0 million (2018: $37.6m) mainly from service fee payments from AstraZeneca and Lilly. 2018 revenues included a one-time $13.5 million milestone payment from Lilly following fruquintinib approval; and

Net loss from our Innovation Platform attributable to Chi-Med of $133.2 million (2018: net loss of $104.4m) resulting from expansion in the development of our eight clinical drug candidates, five of which are now in global development, and establishment of sizable international clinical and regulatory operations.

COMMERCIAL PLATFORM:

Total consolidated sales up 7% (11% at CER32) to $188.9 million (2018: $176.5m) mainly due to continued progress on our Prescription Drugs subsidiary Hutchison Sinopharm33 as well as manufacturing sales and royalties from Elunate during its first full year on the market;

Total consolidated net income from our Commercial Platform attributable to Chi-Med up 9% (13% at CER) to $47.4 million (2018: $43.4m) underpinned by the growing profits of our legacy operations in China as well as Elunate.

FINANCIAL GUIDANCE

In 2019 we performed in-line with our most recent guidance. We provide Financial Guidance for 2020 below.

In 2020, on the broader Innovation Platform, we plan to continue to increase our investment in R&D particularly on clinical development of our main assets in the U.S., Europe and Japan as well as in China (as discussed in the "Product pipeline progress" section below). On the Commercial Platform, we expect to continue to generate cash flow directly through our subsidiaries and via dividends from our joint ventures. We assume at this stage that the financial impact of the recent Covid-19 outbreak will not be material to the Group. Since we cannot predict how the situation will evolve, we will monitor and adjust if new material information emerges.

2020 Guidance

Adjusted (non-GAAP) Innovation Platform segment operating loss

$(180) — (210) million

Adjusted (non-GAAP) Group Net Cash Flows excluding financing activities

$(140) — (160) million

Use of Non-GAAP Financial Measures and Reconciliation — References in this announcement to adjusted Innovation Platform segment operating loss, adjusted Group net cash flows excluding financing activities and financial measures reported at CER are based on non-GAAP financial measures. Please see the "Use of Non-GAAP Financial Measures and Reconciliation" below for further information relevant to the interpretation of these financial measures and reconciliations of these financial measures to the most comparable GAAP measures, respectively.

Conference Call and Audio Webcast Presentation Scheduled Today at 1:00 p.m. GMT / 8:00 a.m. EST / 9:00 p.m. HKT — Investors may participate in the call as follows: +44 20 3936 2999 (U.K.) / 1 845 213 3398 (U.S.) / +852 5808 4954 (Hong Kong), or access a live audio webcast of the call via Chi-Med’s website at www.chi-med.com/investors/event-information/.

Additional dial-in numbers are also available at Chi-Med’s website. Please use participant access code "413486."

FINANCIAL STATEMENTS

Chi-Med will today file with the U.S. Securities and Exchange Commission its Annual Report on Form 20-F.

ANNUAL GENERAL MEETING

The Annual General Meeting of Chi-Med will be held at 4th Floor, Hutchison House, 5 Hester Road, Battersea, London SW11 4AN on Monday, April 27, 2020 at 11:00 a.m.

On March 3, 2020 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company developing potentially life-changing treatments for cancer and other serious diseases, reported it will be presenting at the third annual LD Micro Virtual Conference on Wednesday, March 4 at 1:40 p.m. EST (Press release, Genprex, MAR 3, 2020, View Source [SID1234555117]). Genprex’s Chairman and Chief Executive Officer, Rodney Varner, will lead the company’s presentation and will be answering questions from investors.

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!

To access the live presentation, please use the following link: http://bit.ly/2PFjomt.

"We are delighted to be hosting our third virtual event in order to showcase some of the truly unique names in micro-cap," stated Chris Lahiji, President of LD Micro. "There are many people and companies who are unable to attend our live events due to any number of reasons, so we are happy to offer an additional way for companies to present to investors without taking a lot of time out of their day-to-day operations. While virtual events will never replace the experience of sitting in the same room as other humans, it is a great format for updating the investor community and getting increased exposure."

The conference will be held via webcast and will feature more than 40 companies in the small/micro-cap space.

On March 3, 2020 Exicure, Inc. (NASDAQ:XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) technology, reported full year financial results for year ended December 31, 2019 and provided an update on corporate progress (Press release, Exicure, MAR 3, 2020, View Source [SID1234555116]).

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!

"2019 was a pivotal year for Exicure as we joined strong scientific and clinical progress with the capital resources and distinguished investors necessary to expand our pipeline and build our organization," said Dr. David Giljohann, Chief Executive Officer of Exicure. "Looking ahead, we intend to invest in growing a pipeline of drug candidates targeting neurological indications, as well as advance our Merkel cell and cutaneous squamous cell carcinoma programs into Phase 2 trials. We believe our ongoing clinical progress in immuno-oncology and dermatology has influenced our ability to expand our SNA platform in additional therapeutic areas through collaborative partnerships. Our collaboration with Allergan in hair loss disorders is just one of what we hope will be a number of such partnerships expanding our SNA platform into new therapeutic areas," concluded Dr. Giljohann.

Corporate Progress
Key achievements for Exicure during 2019 include:

Established Friedreich’s ataxia as Exicure’s first neurological indication, being developed in collaboration with the Friedreich’s Ataxia Research Alliance

Announced preliminary data in the ongoing Phase 1b/2 trial of lead immuno-oncology candidate AST-008 in patients with solid tumors

Entered a collaboration agreement with Allergan for two discovery programs in hair loss disorders with $25 million upfront and up to $725 million in potential milestones

Expanded scientific advisory board to include neurology experts Dr. Susan Perlman and Dr. Hank Paulson

Expanded Board of Directors with the addition of Jeffrey L. Cleland of Orpheris, Bali Muralidhar of Abingworth LLP, Bosun Hau of Tybourne Capital Management, and Tim Walbert of Horizon Therapeutics

Raised approximately $90.8 million in gross proceeds from the sale of common stock in two public offerings and up-listed to the NASDAQ Global Market

Pipeline Updates
Neurology

In December of 2019, Exicure announced the development of XCUR-FXN, an SNA-based therapeutic candidate, for the treatment of Friedreich’s ataxia (FA). FA is driven by triplet repeats in the frataxin gene which compromises the patient’s ability to generate adequate levels of frataxin protein. Exicure believes its SNA technology has the potential to address this genetic challenge and that its therapeutic strategy may lead to increases in the frataxin protein. Exicure will be developing XCUR-FXN with guidance from, and in collaboration with, the Friedreich’s Ataxia Research Alliance. Preclinical research is ongoing and IND-enabling studies for XCUR-FXN are expected in late 2020.

In 2020, Exicure expects to continue pre-clinical research on the application of its SNA technology in neurological conditions, building on its early proof-of-concept work with nusinersen and its new therapeutic candidate, XCUR-FXN. Exicure is currently exploring additional neurological conditions, including spinocerebellar ataxia, Batten disease, amyotrophic lateral sclerosis (ALS), and Huntington’s disease.

Immuno-oncology; AST-008

In December of 2019, Exicure announced preliminary results from the Phase 1b study of AST-008 in patients with solid tumors. AST-008 is an investigational SNA consisting of toll-like receptor 9 (TLR9) agonists designed for immuno-oncology applications, and is being evaluated in combination with pembrolizumab in patients with solid tumors. At that time the study had enrolled fourteen patients including five melanoma patients, four Merkel cell carcinoma (MCC) patients, two cutaneous squamous cell carcinoma patients, two head and neck squamous cell carcinoma patients, and one mucosal melanoma patient. Prior to enrolling, most patients had progressive disease on anti-PD-1 or anti-PD-L1 antibodies.

Available data, as of December 11, 2019, showed that AST-008 administration, alone or in combination with pembrolizumab, produced cytokine and chemokine expression and immune cell activation in patient blood indicative of desired immune activation. Of the 4 MCC patients, one patient, who had previously progressed on anti-PD-1 antibody therapy, had confirmed stable disease with decreased target lesion diameters for a period in excess of twelve weeks, while a second MCC patient experienced a target lesion complete response and a confirmed overall partial response longer than 24 weeks. No treatment-related serious adverse events or dose-limiting toxicities have been observed. The most common reported adverse event was injection site reactions.

Exicure is now completing the Phase 1b study and preparing to begin a Phase 2 study in both Merkel cell carcinoma and in cutaneous squamous cell carcinoma. Exicure currently has seven trial sites open and seeks to expand to about fifteen sites.

Collaborations
Exicure entered into a collaboration with Allergan Pharmaceuticals International Limited in late 2019 and is now actively engaged in preclinical research and discovery in two clinical programs related to the treatment of hair loss disorders. Under the terms of the collaboration, Exicure received a $25 million upfront payment and is eligible to receive up to $725 million in potential milestones. In early 2019,

Exicure also entered into a collaboration agreement with Dermelix Biotherapeutics under which Dermelix will develop a targeted therapy for the treatment of Netherton Syndrome (NS).

2019 Financial Results and Financial Guidance
Cash Position: As of December 31, 2019, Exicure had cash and cash equivalents of $48.5 million and short-term investments of $62.3 million for a total of $110.8 million compared to $26.3 million of cash and cash equivalents and no short-term investments as of December 31, 2018. In 2019, Exicure raised approximately $90.8 million in gross proceeds from the sale of common stock and received a $25 million upfront payment in connection with the Collaboration Agreement with Allergan.

Research and Development Expense: Research and development expense was $19.3 million for the year ended December 31, 2019 compared to $14.1 million for the year ended December 31, 2018. The increase in research and development expense of $5.2 million was primarily due to higher platform and discovery-related expenses of $4.7 million, higher employee-related expense of $0.9 million and higher facilities, depreciation, and other expenses of $0.2 million, partially offset by a net decrease of $0.6 million in costs related to our clinical development programs. The increase in platform and discovery-related expenses is mostly due to a license fee of $3.8 million paid to Northwestern University in connection with the $25.0 million upfront payment received from Allergan.

General and Administrative Expense: General and administrative expense was $8.6 million for the year ended December 31, 2019 and $7.8 million for the year ended December 31, 2018, an increase of $0.8 million. This increase was primarily due to higher compensation and related expenses, recruiting fees in connection with adding two new board members, higher D&O insurance premiums, Nasdaq listing costs and lease costs associated with our Cambridge, MA office. These increased costs were partially offset by reductions in legal and other transaction costs.
Net Loss: Net loss was $26.3 million for the year ended December 31, 2019, compared to net loss of $22.4 million for the year ended December 31, 2018, an increase in loss of $3.9 million. Net loss reflects the changes in expenses discussed above and is offset by an increase in revenue of $1.2 million for the year ended December 31, 2019 compared to revenue for the year ended 2018. Revenue in 2019 was primarily related to the Dermelix Collaboration.
Cash Runway Guidance: Exicure believes that, based on its current operating plans and as of the date of this press release, its existing cash and cash equivalents as of December 31, 2019 is sufficient to meet its anticipated cash requirements into early 2022.

About Friedreich’s Ataxia (FA)
FA is a rare, degenerative, life-shortening neuro-muscular disorder that affects children and adults, and involves the loss of strength and coordination usually leading to wheelchair use, diminished vision, hearing and speech, scoliosis, increased risk of diabetes, and a life-threatening heart condition. There are no FDA-approved treatments. An estimated 5,000 patients in the US and 15,000 patients worldwide are affected by FA.

About FARA
The Friedreich’s Ataxia Research Alliance (FARA) is a 501(c)(3), non-profit, charitable organization dedicated to accelerating research leading to treatments and a cure for Friedreich’s ataxia. www.CureFA.org.

On March 3, 2020 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months and year ended December 31, 2019 and provided a corporate update (Press release, DURECT, MAR 3, 2020, View Source [SID1234555115]).

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!

Total revenues were $10.7 million and net loss was $4.2 million for the three months ended December 31, 2019 as compared to total revenues of $3.6 million and net loss of $7.3 million for the three months ended December 31, 2018.

Total revenues were $29.6 million and net loss was $20.6 million for the year ended December 31, 2019, compared to total revenues of $18.6 million and net loss of $25.3 million for the year ended December 31, 2018.

At December 31, 2019, cash and investments were $64.8 million, compared to cash and investments of $34.5 million at December 31, 2018. Debt at December 31, 2019 was $20.3 million, compared to $20.5 million at December 31, 2018.

"The highlight of the year for DURECT in 2019 was achieving positive results from our DUR-928 Phase 2a alcoholic hepatitis (AH) study, which were featured in multiple presentations at the Liver Meeting 2019, including a late-breaking oral presentation by Dr. Tarek Hassanein," stated James E. Brown, D.V.M., President and CEO of DURECT. "In addition, we have already exceeded our 60 patient enrollment target in the ongoing NASH trial, and the last patient is scheduled to begin the 28-day dosing period next week. We are on track to announce top-line NASH data mid-year. We are also making steady progress toward starting a Phase 2b AH clinical trial by mid-year. In January 2020, the FDA held an Advisory Committee meeting to discuss our POSIMIR NDA resubmission. Subsequently, we have continued to interact with FDA as they continue their review."

Potential major milestones in 2020:

Initiation of Phase 2b trial of DUR-928 in AH: mid-year

Reporting top-line data from the DUR-928 one-month daily dose trial in NASH: mid-year

POSIMIR FDA decision

Commercial partnership if POSIMIR is approved

New license and collaboration agreements

Update on Selected Programs and Transactions:

Epigenetic Regulator Program. DUR-928, the lead product candidate in the Company’s Epigenetic Regulator Program, is an endogenous, orally bioavailable, first-in-class small molecule, which may have broad applicability in acute organ injuries such as AH, and in chronic liver diseases such as non-alcoholic steatohepatitis (NASH).

Clinical Trials

Alcoholic Hepatitis (AH)

During 2019, we completed a Phase 2a clinical trial of DUR-928 in patients with AH. The study results were presented as a late-breaking oral presentation at The Liver Meeting 2019 by Dr. Tarek Hassanein, one of the trial’s principal investigators. In a separate poster presentation, Dr. Craig McClain presented additional comparative data from the Phase 2a clinical trial of DUR-928 and a control group of severe AH patients treated with corticosteroids in a contemporaneous AH trial conducted at University of Louisville. Additionally, the DUR-928 results were selected for inclusion in the "Best of The Liver Meeting" summary slide deck in the Alcohol-related Liver Disease category. Inclusion in this slide deck is considered a singular honor and indicates the high level with which the AASLD review committee regarded this study.

All 19 patients treated with DUR-928 in the AH trial survived the 28-day follow-up period and there were no drug-related serious adverse events. Patients treated with DUR-928 had a statistically significant reduction from baseline in bilirubin at days 7 and 28, and model of end-stage liver disease (MELD) at day 28. Lille scores were also statistically significantly lower than those from a well-matched group of patients in a contemporary trial as well as from several published comparable historical control groups. Seventy four percent of all DUR-928 treated patients and 67% of those with severe AH were discharged from the hospital within four days of receiving a single dose of DUR-928.

DUR-928 AH Phase 2a trial design: The open-label, dose escalation, multi-center study was designed to determine the safety, pharmacokinetics and pharmacodynamic signals of DUR-928 in AH patients following treatment. This included assessing liver biochemistry, biomarkers, and prognostic scores such as the Lille score. Final enrollment included 19 patients with moderate and severe AH, who were administered DUR-928 intravenously at three different doses. Eight patients (four moderate and four severe) were dosed at 30 mg, seven patients (three moderate and four severe) were dosed at 90 mg and four patients (all severe) were dosed at 150 mg. After being discharged on day two, one patient did not return for the scheduled day 7 and day 28 follow-up visits (this patient did survive through day 28); therefore Lille, bilirubin and MELD data reported above are based on 18 patients.

AH is an acute form of alcoholic liver disease (ALD) associated with long-term heavy intake of alcohol, and often occurs after a recent period of increased alcohol consumption. AH is typically characterized by recent onset jaundice and hepatic failure. An analysis of 77 studies published between 1971 and 2016, which included data from a total of 8,184 patients, showed the overall mortality from AH was 26% at 28 days. According to the most recent data provided by the Agency for Healthcare Research and Quality (AHRQ), a part of the US Department of Health and Human Services (HHS), there were over 117,000 hospitalizations for patients with alcoholic hepatitis in 2016. From a recent publication analyzing the mortality and costs associated with alcoholic hepatitis, the cost per patient is estimated at over $50,000 in the first year. ALD is one of the leading causes of liver transplants in the U.S., costing over $800,000 per patient.

We are working with the FDA and our advisors to finalize the design of a multi-center, international, randomized, double blind, placebo-controlled Phase 2b clinical trial of DUR-928 in AH patients. We are planning to initiate the trial in mid-2020. Based on our current working assumptions related to trial design, number of clinical trial sites and enrollment rates, top-line data for this trial may be available in 2022.

Non-Alcoholic Steatohepatitis (NASH)

We have exceeded our 60 patient enrollment target in the ongoing NASH trial, and the last patient is scheduled to begin the 28-day dosing period next week. The trial is a Phase 1b randomized and open-label clinical study being conducted in the U.S. to evaluate safety, pharmacokinetics and signals of biological activity (including clinical chemistry and biomarkers as well as liver fat content and liver stiffness by MRI and ultrasonic imaging, respectively) of DUR-928 in NASH patients with stage 1-3 fibrosis. DUR-928 (at

doses of 50 mg QD, 150 mg QD or 300 mg BID) is administered orally for 28 consecutive days with approximately 20 or more patients per dose group for a total of over 60 patients in the trial.

We expect all patients to complete their dosing and follow up visits in the first half of 2020 and expect to announce top-line study results mid-year.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in both children and adults. It is estimated that NAFLD affects approximately 30% to 40% of adults and 10% of children in the United States. NASH, a more severe and progressive form of NAFLD, is one of the most common chronic liver diseases worldwide, with an estimated prevalence of 3-5% globally. No drug is currently approved for NAFLD or NASH.

Psoriasis

In January 2020, we announced the results from a Phase 2a clinical trial of DUR-928 in patients with mild to moderate plaque psoriasis. Twenty-two patients completed the study, applying DUR-928 topically to the plaque on one arm and the vehicle (placebo) to a similar plaque on the other arm daily for 28 days. DUR-928 did not demonstrate a benefit over vehicle (placebo) based on Investigator’s Global Assessment (IGA), or in any of the secondary analyses, including Local Psoriasis Severity Index (LPSI). However, at the end of the 4-week daily application period, plaques in both the DUR-928 and vehicle treatment groups were significantly improved over baseline with respect to both IGA and LPSI scores. In fact, 90% of plaques in both groups had at least a 1 point reduction in LPSI score after the 4-week daily application period as compared to baseline. Daily topical application of DUR-928 was well tolerated with no meaningful differences in adverse events between the treatment and vehicle (placebo) groups. Based on the top-line data, we do not plan to continue development of topical DUR-928 in psoriasis at this time and will focus our near- term development activities on AH and NASH.

POSIMIR (bupivacaine extended-release solution) Post-Operative Pain Relief Depot. POSIMIR is the Company’s investigational post-operative pain relief depot that uses the Company’s patented SABER technology and is designed to deliver bupivacaine to provide up to 3 days of pain relief after surgery.

After a comprehensive review of the POSIMIR program in light of the issues raised by the FDA in our communications with them, including the Complete Response Letter (CRL), we prepared and submitted a response to the CRL in June 2019. The FDA initially assigned a user fee goal date of December 27, 2019, but subsequently scheduled a meeting of the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) for January 16, 2020; a new user fee goal date has not been assigned. At the meeting, six Advisory Committee members voted to recommend that the efficacy, safety, and overall risk-benefit profile of POSIMIR support approval, while six did not recommend approval based on the information presented. Although the FDA considers the recommendations of the Advisory Committee, the recommendations by the panel are non-binding.

Since the Advisory Committee meeting, we have continued to interact with the FDA as they continue their review.

The efforts to evaluate the program, develop a strategy for filing the response, and preparing the response, have been under the direction of Dr. Lee Simon, who was formerly the FDA’s Division Director of Analgesic, Anti-inflammatory and Ophthalmologic Drug Products. Dr. Simon also led our preparation efforts for the Advisory Committee meeting.

POSIMIR has not been approved by the FDA for marketing in the U.S. for any indication and there can be no assurance that FDA will approve the planned submission described above.

Gilead Collaboration. The investigational long-acting injectable HIV product using DURECT’s SABER technology under development with Gilead is currently being re-formulated and will undergo additional pre-clinical development work.

Debt Amendment. In December 2019, the Company amended its existing $20 million term loan with Oxford Finance such that principal payments will commence 18 months later than previously scheduled (i.e., commencing December 1, 2021 rather than June 1, 2020) and the final maturity date has been moved back by 18 months (i.e., from November 1, 2022 to May 1, 2024). The interest rate and final payment remain unchanged, and the Company paid Oxford Finance an amendment fee of $825,000.

Earnings Conference Call

We will host a conference call today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss fourth quarter 2019 results and provide a corporate update:

Toll Free:877-407-0784

International:201-689-8560

Conference ID:13698601

Webcast:View Source

A live audio webcast of the presentation will be also available by accessing DURECT’s homepage at www.durect.com and clicking "Investors." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under "Event Calendar" in the "Investors" section.