On November 14, 2017 Purdue Pharma L.P. reported completion of significant oncology related investments as part of its ongoing efforts to diversify its scientific research into areas of high unmet medical need (Press release, Purdue Pharma, NOV 14, 2017, View Source [SID1234527505]). Through these investments, executed over a multi-year period and capped recently in 2017, Purdue is establishing a portfolio of drug candidates with the potential to deliver new cancer therapies to patients within the next five years.

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"With this formal entry into oncology research and development, Purdue is evolving as a company and renewing its foundational commitment to bring important new medicines to patients and physicians who need them," said Craig Landau, president and CEO, Purdue Pharma. "We are excited by the opportunity and the potential to make meaningful contributions to the field of cancer medicine."

In assembling this portfolio, Purdue now has four drug candidates in development for multiple cancer types:

EDO-S7.1, a novel topoisomerase inhibitor, is designed to work by metabolizing into its active form through enzymes in the gastrointestinal tract that are particularly active in cancer cells. In an interim analysis of a phase 2 trial in patients with therapy refractory advanced biliary tract cancers, the trial met the primary endpoint of rate of disease control (DCR) after first stage. In the trial, commonly observed drug related adverse events were: myelosuppression (including grade 3-4 neutropenia and thrombocytopenia), infection, alopecia, fatigue, nausea, and abdominal pain.1
EDO-S101, also known as tinostamustine, is a novel, first-in-class alkylating deacetylase inhibitor (AK-DACi) compound currently advancing through phase 1 human trials. Preclinical studies suggest that tinostamustine delivers both alkylating activity and pan-histone deacetylase (HDAC) inhibition to simultaneously damage DNA and block damage repair in cancer cells. The development programs for this drug candidate are investigating its potential utility in both solid and hematologic tumors.
EDO-B776 and EDO-B278 are two late pre-clinical stage antibody-drug conjugates. EDO-B776 is being studied for its potential to target the cancer antigen 125 (CA-125) in ovarian cancer. EDO-B278 is an antibody-drug conjugate targeting the human tissue factor and is in development for various solid tumors.
Research on these drug candidates is being directed on behalf of Purdue by Mundipharma EDO GmbH, part of the Mundipharma network of independent associated companies.

"We are pleased to collaborate with Purdue Pharma on the development of these important compounds," said Dr. Thomas Mehrling, chief executive officer, EDO. "Purdue’s strong experience developing novel treatments will translate well to oncology and we are confident that this will be a successful partnership."

Purdue will also continue to selectively seek additional oncology product assets through licensing and acquisition, and the company will maintain a priority interest in candidates with mechanisms complementary to emerging immuno-oncology based treatment paradigms.

On November 14, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that it has entered into a global collaboration with Bayer to develop and commercialize larotrectinib and LOXO-195, Loxo Oncology’s franchise of highly selective TRK inhibitors for patients with TRK fusion cancers (Press release, Loxo Oncology, NOV 14, 2017, View Source [SID1234522033]).

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Under the terms of the agreement, Loxo Oncology will receive a $400M upfront payment. Loxo Oncology is eligible for $450M in milestone payments upon larotrectinib regulatory approvals and first commercial sale events in certain major markets and an additional $200M in milestone payments upon LOXO-195 regulatory approvals and first commercial sale events in certain major markets.

"This is a transformational collaboration for the company as we prepare for commercialization," said Jacob Van Naarden, chief business officer of Loxo Oncology. "Bayer has a history of successful co-promotion efforts with emerging biopharmaceutical companies and we are confident that their oncology team has the global reach and expertise, including an existing field force dedicated to cancer, to complement our existing commercial plans. We look forward to working with Bayer and believe that together we can bring our TRK inhibitors to more patients more quickly."

"We see great potential in larotrectinib and moreover the follow-on compound LOXO-195 which may provide additional benefit for patients who might progress on an initial TRK inhibition therapy. These agents have the potential to fulfill the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach for patients," said Robert LaCaze, executive vice president and head of the Oncology Strategic Business Unit at Bayer.

Loxo Oncology will lead global development activities and United States (U.S.) regulatory activities. Bayer will lead ex-U.S. regulatory activities, and worldwide commercial activities. Globally, Loxo Oncology and Bayer will share development costs on a 50/50 basis. In the U.S., where Loxo Oncology and Bayer will co-promote the products, the parties will share commercial costs and profits on a 50/50 basis. Bayer will pay Loxo Oncology a $25M milestone upon achieving a certain U.S. net sales threshold. Outside of the U.S., where Bayer will commercialize, Bayer will pay Loxo Oncology tiered, double-digit royalties on net sales, and sales milestones totaling $475M. Bayer will book revenues worldwide.

Loxo Oncology was advised by Fenwick and West in the transaction.

Conference Call Information
Loxo Oncology will host a conference call today at 8:00 a.m. ET to discuss this collaboration announcement. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 8077486. A replay will be available shortly after the conclusion of the call and archived on the company’s website for 30 days following the call.

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent independently-reviewed confirmed overall response rate (ORR) and an 80 percent investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation, Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

About LOXO-195
LOXO-195 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that have acquired resistance to initial TRK therapy such as larotrectinib. Though drugs such as larotrectinib can induce durable responses in these patients, the cancer may eventually begin to grow again. This phenomenon is called "acquired resistance," in that the cancer has acquired features conferring resistance to the initial therapy that was once effective. Emerging data in the field of TRK inhibition suggest that acquired resistance may emerge due to TRK kinase point mutations, such as those in the solvent front domain, xDFG domain, or gatekeeper region. LOXO-195 was designed to address these new point mutations and induce a new response in the patient’s cancer. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or email [email protected].

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

On November 14, 2017 Audentes Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology company focused on developing and commercializing gene therapy products for patients living with serious, life-threatening rare diseases, reported its financial results for the quarter ended September 30, 2017, and provided an update on the company’s recent achievements and anticipated upcoming milestones (Press release, Audentes Therapeutics, NOV 14, 2017, View Source;p=RssLanding&cat=news&id=2316918 [SID1234522069]).

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"I am pleased with the excellent progress we have made to advance our pipeline toward key value inflection milestones, including the recent completion of dosing for the first cohort in ASPIRO, the Phase 1 / 2 clinical study of AT132 for the treatment of XLMTM," stated Matthew R. Patterson, President and Chief Executive Officer. "While we are only weeks into the study, we are encouraged by the progress to date and look forward to sharing preliminary safety and efficacy data from the first cohort of patients in early January 2018. This will be the first of many catalysts over the coming months as we execute on our ambitious goal of creating the world’s leading gene therapy company focused on developing a multi-product pipeline to treat serious, life-threatening rare diseases with high unmet medical need."

Recent Achievements & Upcoming Key Events

AT132 for X-Linked Myotubular Myopathy:
Completed dosing of the first cohort of patients in ASPIRO, the Phase 1 / 2 clinical study of AT132. To date, AT132 has been well-tolerated by all patients with no significant treatment-related safety signals.
Announced interim results from INCEPTUS, a prospective natural history run-in study in patients with XLMTM. The primary objectives of INCEPTUS are to characterize the clinical condition of children with XLMTM, identify subjects for potential enrollment in ASPIRO, and serve as a longitudinal baseline and with-in patient control for ASPIRO. Preliminary results from INCEPTUS confirm the significant neuromuscular and respiratory deficits experienced by XLMTM patients, and provide insight into the relevance and sensitivity of assessments used in the ASPIRO study.
Received approval for the Clinical Trial Authorisation (CTA) application for AT132 from the United Kingdom’s (U.K.) Medicines and Healthcare Products Regulatory Agency (MHRA), and anticipate initiation of U.K. enrollment in the first quarter of 2018 for ASPIRO.
Plan to report preliminary clinical data from ASPIRO in early January 2018
AT342 for Crigler-Najjar:
Plan to discuss initial results of LUSTRO, the prospective natural history run-in study being conducted in patients with Crigler-Najjar Syndrome, on the third quarter 2017 earnings call
Plan to dose first patient in VALENS, the Phase 1 / 2 clinical study of AT342, in the first quarter of 2018, and to report preliminary data in the second quarter of 2018
Received approval for the CTA application for AT342 from the MHRA, and anticipate initiation of U.K. enrollment in the first quarter of 2018 for VALENS
AT982 for Pompe Disease:
Conducting a comprehensive in vivo construct selection and dose-ranging study evaluating a range of AAV8 and AAV9 vector constructs designed to express GAA selectively within tissues relevant to Pompe disease, including skeletal muscle, motor neurons and liver. Candidate vectors are being evaluated across a broad range of neuromuscular function and biochemical endpoints at multiple dose levels.
Plan to select optimal construct and file IND in the first half of 2018
AT307 for CASQ2-CPVT:
Completed successful pre-IND/CTA meetings with both the U.S. Food and Drug Administration (FDA) and MHRA, and have incorporated input from both agencies into IND filing plans
Expect to file IND in the first quarter of 2018
Appointed Fulvio Mavilio, Ph.D. as Vice President Scientific Affairs, Europe. Dr. Mavilio is an internationally recognized scientific leader who has made important contributions to the field of molecular genetics and gene therapy for rare diseases.
Third Quarter 2017 Financial Results

Cash Position: As of September 30, 2017, Audentes had cash, cash equivalents and short-term investments of approximately $156.0 million.
R&D Expenses: Research and development expenses were $20.9 million for the third quarter of 2017 compared to $12.5 million for the same period in 2016, an increase of $8.4 million. The increase was primarily due to increased research and development expenses for our AT132 and AT307 programs, increases in our research and development headcount and higher facility costs as we made additional investments in our manufacturing and research facilities. For the nine months ended September 30, 2017, research and development expenses were $54.2 million compared to $32.2 million for the same period in 2016.
General and Administrative: General and administrative expenses were $4.3 million for the third quarter of 2017 compared to $2.9 million for the same period in 2016, an increase of $1.4 million. The increase was primarily due to increased G&A headcount and increases in other G&A expenses related to regulatory compliance and operations as a public company. For the nine months ended September 30, 2017, general and administrative expenses were $12.1 million compared to $8.0 million for the same period in 2016.
Net Loss: Net loss was $25.0 million for the third quarter of 2017, compared to a net loss of $15.4 million for the same period in 2016. For the nine months ended September 30, 2017, our net loss was $65.9 million as compared to $40.0 million for the same period in 2016.
Conference Call
At 4:30 p.m. Eastern Time today, Audentes management will host a conference call and a simultaneous webcast to discuss its third quarter 2017 financial results and provide a corporate update. To access a live webcast of the conference call, please visit the Investor and Media page of the Audentes website at www.audentestx.com. Alternatively, please call 1-833-659-8620 (U.S.) or 1-409-767-9247 (international) and dial the conference ID 2599735 to access the call.

A replay of the webcast will be available on the Audentes website for approximately 30 days.

On November 14, 2017 Exicure, Inc., a Delaware corporation (the "Company"), the pioneer in gene regulatory and immunotherapeutic drugs utilizing three-dimensional Spherical Nucleic Acid (SNA) constructs, reported its financial results for the third quarter ended September 30, 2017 (Press release, Celsion, NOV 14, 2017, View Source [SID1234522047]).

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"The third quarter was a transformational period for the Company. We continued to advance two SNA drug candidates toward their Phase 1 clinical trials and began our life as a public company," said David Giljohann, Chief Executive Officer of the Company. "We also strengthened our financial position with an initial private placement of approximately $20 million in gross proceeds, followed in the fourth quarter with two subsequent closings, raising an additional approximately $11 million in gross proceeds. This financing will support the clinical development of our lead programs where we have continued our strong progress. By early 2018 we look forward to having three clinical stage drugs."

The Merger and Private Placement

The Merger—On September 27, 2017, we announced the completion of a reverse merger transaction with Max-1 Acquisition Corporation. Immediately after the completion of the merger, Max-1 Acquisition Corporation changed its name to Exicure, Inc. and continued the historical business of Exicure Operating Company, our wholly owned subsidiary. In connection with the merger, we expect to commence trading on the OTC Markets in early 2018.

In accordance with "reverse merger" or "reverse acquisition" accounting treatment, our historical financial statements as of period ends, and for periods ended, prior to the reverse merger will be replaced with the historical financial statements of Exicure Operating Company prior to the reverse merger, in all future filings with the U.S. Securities and Exchange Commission, or SEC. The consolidated financial statements after completion of the reverse merger will include the assets, liabilities and results of operations of the combined company from and after the closing date of the reverse merger.

The Private Placement— On September 26, 2017, we sold 6,767,360 shares of our common stock at a purchase price of $3.00 per share, raising thereby approximately $20.3 million in gross proceeds pursuant to an initial closing of a private placement offering.

Subsequently, on October 27, 2017, we sold 1,878,335 of our common shares at a purchase price of $3.00 per share for gross proceeds of approximately $5.6 million in the first subsequent closing of the private placement. On November 2, 2017, we sold 1,858,501 of our common shares at a purchase price of $3.00 per share for gross proceeds also of approximately $5.6 million in the second subsequent closing of the private placement. In aggregate we have raised approximately $31.5 million of gross proceeds through the private placement.

Third Quarter Business Update

AST-008—In the third quarter of 2017, we received authorization from the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom to conduct a Phase 1 clinical trial with AST-008 in the United Kingdom. AST-008, an SNA consisting of a TLR9 agonist, is being developed for immuno-oncology applications. While we ultimately plan to clinically advance AST-008 in combination with checkpoint inhibitors, the Phase 1 clinical trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of AST-008 by subcutaneous administration in healthy volunteers. We expect to start the Phase 1 clinical trial during the fourth quarter.

XCUR17—During the third quarter of 2017, we submitted a clinical trial application to conduct a Phase 1 clinical trial for XCUR17 to the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the medical regulatory body in Germany. XCUR17 is an antisense SNA that targets the mRNA encoding IL-17RA, a protein that is considered essential in the initiation and maintenance of psoriasis. Our proposed Phase 1 trial is a microplaque study in patients with mild to moderate psoriasis. We are currently working with BfArM to finalize the trial protocol.

Purdue Pharma L.P. Collaboration—During the third quarter of 2017, the ongoing Phase 1b clinical trial for AST-005 was completed. AST-005 is an SNA containing TNF antisense oligonucleotides and is intended to be applied in a gel to psoriatic lesions. The Phase 1b clinical trial was conducted in Germany and was intended to evaluate the safety and tolerability of AST-005. We expect topline results from this clinical trial to be available in late 2017.

Third Quarter 2017 Financial Results and Financial Guidance

Cash Position—As of September 30, 2017 Exicure had cash and cash equivalents of $22.9 million compared to $19.6 million as of December 31, 2016. Gross proceeds from the issuance of common stock during the third quarter were $20.3 million with net proceeds of $17.1 million.

Research and development (R&D) expenses—R&D expenses for the third quarter were $3.5 million compared to $2.4 million for the same period in 2016. This increase was due primarily to the costs associated with preparing both AST-008 and XCUR17 for clinical trials.

General and administrative (G&A) expenses—General and administrative expense was $1.3 million for the third quarter compared to $0.8 million for the same period in 2016. This increase in expenses was driven primarily by an increase in non-cash stock compensation costs and certain costs incurred in connection with our merger and private placement.

Net Loss—Net loss for the third quarter was $2.3 million compared to a net loss of $3.5 million for the same period in 2016. The decrease in net loss was driven principally by earning $2.5 million in collaboration revenue attributable to our collaboration with Purdue compared to no revenue for the same period in 2016. The increase in revenue was offset by the increase in R&D expenses described above.

Guidance—We believe that our cash and cash equivalents, as of the date of this press release, are sufficient to fund our current operating plans into 2019.

On November 14, 2017 Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company focused on developing novel oncology and hematology therapeutics, reported that management will be presenting at the 29th Annual Piper Jaffray Healthcare Conference on Tuesday, November 28, 2017 at 4:00 pm ET at the Lotte New York Palace Hotel (Press release, Aptevo Therapeutics, NOV 14, 2017, View Source;p=RssLanding&cat=news&id=2316919 [SID1234522070]).

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A live audio webcast of the presentation can be accessed at www.aptevotherapeutics.com under the ‘Investors’ section of the website, under ‘Events.’ An audio reply of the webcast will be available approximately 2 hours following the live webcast.