On March 16, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported financial and operational highlights for the fourth quarter and year-ended Dec. 31, 2019 (Press release, Turning Point Therapeutics, MAR 16, 2020, View Source [SID1234564377]).

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"I am very pleased with all we accomplished in 2019, and in 2020 we are focused on clinical trial and pipeline advancement," said Athena Countouriotis, M.D., president and chief executive officer. "As we advance our clinical programs with site activations and patient enrollment across our three clinical stage assets, we remain pleased with our progress but are in close contact with our CROs and sites as we navigate and assess the impact of COVID-19 on our studies and current timelines."

Fourth quarter 2019 and recent highlights include:

Ongoing site activations and enrollment in the Phase 2 registrational portion of the TRIDENT-1 study of repotrectinib. The study is planned at approximately 100 global sites with enrollment of approximately 320 ROS1-positive advanced non-small cell lung cancer (NSCLC) and NTRK-positive advanced solid tumor patients. Approximately 40 percent of planned sites are now active.

Fast Track designation granted by the U.S. Food and Drug Administration for the treatment of ROS1-positive advanced NSCLC patients who have been previously treated with one prior line of platinum-based chemotherapy and one prior line of a ROS1 tyrosine kinase inhibitor (TKI). There are currently no approved targeted therapies for TKI-pretreated ROS1-positive NSCLC patients.

Ongoing progress in the Phase 1 study of TPX-0022, Turning Point’s MET/CSF1R/SRC inhibitor; and Phase 1/2 study of TPX-0046, Turning Point’s RET/SRC inhibitor trial. Both studies have now enrolled both TKI-naïve and pretreated patients. For TPX-0046, the company previously announced that enrollment had also included RET-positive patients with solvent-front mutations previously treated with other investigational RET inhibitors.

Nomination of TPX-0131, a next-generation ALK inhibitor candidate. TPX-0131 has been designed with a compact macrocyclic structure and in preclinical studies has been shown to potently inhibit wildtype ALK and numerous ALK mutations, in particular the clinically observed G1202R solvent-front mutation and G1202R/L1196M compound mutation.

Acceptance of three abstracts for presentation at the AACR (Free AACR Whitepaper) Annual Meeting, including preclinical repotrectinib combination data and preclinical data for TPX-0131. In light of the postponement of AACR (Free AACR Whitepaper)’s Annual Meeting, these data are planned for presentation by the company in the second quarter.

Naming Siegfried Reich, Ph.D. as executive vice president and chief scientific officer. Dr. Reich has over 25 years of pharmaceutical and biotech experience developing more than 20 drug candidates, including the approved drugs Viracept for HIV and the tyrosine kinase inhibitor Inlyta for the treatment of kidney cancer.
Fourth Quarter Financial Update
Operating expenses for the fourth quarter were $23.1 million compared to $9.5 million for the fourth quarter of 2018 and $22.1 million for the third quarter of 2019. The $13.6 million year-over-year increase was primarily due to increased development spend for repotrectinib, TPX-0022 and TPX-0046 as well as personnel expenses that included $4.2 million in non-cash stock-based compensation. Fourth-quarter net cash used in operating activities totaled $14.1 million.

For the year, operating expenses totaled $77.7 million compared to $25.6 million during 2018. The $52.1 million increase was driven by development expenses for repotrectinib, TPX-0022 and TPX-0046 and personnel expenses that included $12.7 million in non-cash stock-based compensation. Net cash used in operating activities was $57.8 million.

Cash, cash equivalents and marketable securities at Dec. 31, 2019 totaled $409.2 million, a decrease of $14.4 million from Sept. 30, 2019. The company continues to project its cash position funds current operations beyond 2021.

Upcoming Milestones
Key milestones anticipated through 2020 include:

Presenting preclinical repotrectinib combination data and preclinical data for TPX-0131 in the second quarter.

Early interim data from initial patients in some of the registrational cohorts of the repotrectinib TRIDENT-1 Phase 2 study during the second half of the year.

Early interim data from initial patients treated with TPX-0022 during the second half of the year.

Submitting the IND for TPX-0131 by early 2021.
Webcast and Conference Call
Turning Point Therapeutics will not host a Quarterly Update conference call this quarter. The company has posted an updated investor presentation on the "Investors" section of tptherapeutics.com.

On March 16, 2020 Beijing Tide Pharmaceutical Co., Ltd. (Tide), a subsidiary of Sino Biopharmaceutical Limited, and Insilico Medicine, an artificial intelligence company developing end-to-end drug discovery pipelines, reported that they are entering a collaboration, applying artificial intelligence (AI) technology to drug discovery, to jointly accelerate the process for multiple types of cancer treatment (Press release, Beijing Tide Pharmaceutical, MAR 16, 2020, View Source [SID1234555626]). This agreement includes an upfront payment, milestone payments, and royalties based on the sales of the products from the collaboration.

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"Tide is the second pharma company of Sino Biopharmaceutical Limited working with Insilico Medicine. We see a great potential of applying AI technology to drug discovery and healthcare sections, and we will invest more in AI applications," said Sino Biopharmaceutical Limited’s Chairlady Theresa Tse.

Alex Zhavoronkov, CEO of Insilico Medicine, is likewise excited about the joint effort: "This collaboration was established for a single purpose: to support combined efforts to find a cure for and eliminate cancer. By using our resources and working with others dedicated to a common cause, there is a hope that together we can beat this disease."

Tide is a high-tech pharmaceutical enterprise in China with the capability of developing, manufacturing as well as marketing series of targeted drugs. Through years of experience, Tide has been identified as one of the innovation pilot enterprises, committed to innovation in science and technology. With the help of Insilico Medicine’s AI platform, the new era of research and development of the Pharmaceutical industry has arrived. Tide Pharmaceutical and Insilico Medicine look forward to a long term and win-win partnership from the joint alliance of both companies.

Last September Insilico Medicine published a landmark paper in Nature Biotechnology demonstrating the application of its generative tensorial reinforcement learning systems to generate novel molecules for kinases in just 46 days including experimental validation which was widely covered by the press. The emerging AI technologies are expected to improve drug discovery process, and Tide commits to be a part of the AI revolution.

On March 16, 2020 Bridge Medicines and The Rockefeller University reported an exclusive license agreement to develop novel inhibitors of ENL-YEATS for the treatment of acute leukemias such as Acute Myelogenous Leukemia (AML) and potentially solid tumors (Press release, Bridge Medicines, MAR 16, 2020, View Source [SID1234555625]).

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ENL-YEATS is an epigenetic "reader" protein that emerged from breakthrough science conducted in the laboratory of Lasker Award winner C. David Allis, Ph.D. The work was led by scientist Liling Wan, Ph.D., who was a postdoctoral fellow in the Allis lab at the time. Dr. Allis is the Joy and Jack Fishman Professor, Laboratory of Chromatin Biology and Epigenetics; Dr. Wan was recently appointed Assistant Professor of Cancer Biology and Assistant Investigator of the Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania.

Epigenetic pathways have been shown to regulate cancer cell proliferation and growth, which have recently proven to be successful drug targets. Drs. Wan and Allis found that ENL-YEATS was essential for leukemogenesis and leukemia maintenance by assuring transcription of several oncogenes, including MYC, a regulator gene.

The researchers also discovered a role for ENL-YEATS in Wilms Tumor, a rare kidney cancer found in children, suggesting that ENL-YEATS may be a driver in tumor types beyond acute leukemias.

The Tri-Institutional Therapeutics Discovery Institute, Inc. (Tri-I TDI) advanced the pioneering discoveries from the Allis Laboratory into early-stage drug molecules. Tri-I TDI’s mission is to work with innovative scientists at its founding institutions, The Rockefeller University, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medicine, in a close collaboration with Takeda Pharmaceutical Company Ltd, to accelerate the discovery of new drug molecules.

For this ENL-YEATS program, the scientists at Tri-I TDI, in collaboration with Drs. Wan and Allis, were able to synthesize promising, patented, new molecules that may represent future new drug products. Bridge Medicines will further develop and advance these molecules through preclinical and clinical trials in an effort to bring a new treatment to patients.

"The ENL-YEATS discovery is a major scientific advancement in the area of cancer treatment, and we are thrilled to bring this important program into our portfolio," said Bill Polvino, CEO of Bridge Medicines. "We are encouraged by the promising data developed by these premier academic scientists and look forward to rapidly accelerating the development of this program, in keeping with our mission of translating brilliant discoveries into innovative medicines."

Dr. Allis added, "The ENL-YEATS program offers great promise and hope for patients with AML and Wilms Tumor. We are gratified to have Bridge Medicines partner with us in advancing this program and look forward to seeing it develop into a successful epigenetic therapy to combat these and potentially other diseases."

About AML
Acute Myeloid Leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood, interfering with normal blood cells. AML progresses rapidly and is typically fatal within weeks or months if left untreated. Current standard of care is chemotherapy, followed by radiation therapy or stem cell transplant. In 2015, AML affected about one million people and resulted in 147,000 deaths globally, and accounts for about 1.8% of cancer deaths in the United States.

About Wilms Tumor
Wilms Tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children. It is named after Max Wilms, a German surgeon (1867-1918) who first described it. Approximately 650 cases are diagnosed in the U.S., annually. The majority of cases occur in children with no associated genetic syndromes; however, a minority of children with Wilms Tumor have a congenital abnormality.

On March 16, 2020 Medivir AB (Nasdaq Stockholm: MVIR) reported that it has entered into a license agreement with US biotech company Tango Therapeutics for one of Medivir’s preclinical research programs (Press release, Medivir, MAR 16, 2020, View Source [SID1234555624]). Under the terms of the agreement, Medivir will receive an undisclosed upfront payment and is eligible to receive multiple undisclosed development and commercial milestones as well as low single-digit royalties on future products.

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"We are pleased to see one of our promising preclinical assets finding a new home for further exploration by a very exciting company" said Dr Christina Herder, EVP & COO of Medivir.

"Synthetic lethality as the basis for a cancer drug target discovery engine holds tremendous promise, exemplified by the number of novel context-dependent cancer drug targets we have discovered using this approach in the past few years," said Barbara Weber, MD, Tango’s President and Chief Executive Officer. "In-licensing this program from Medivir will help us to capitalize on a novel synthetic lethal interaction and accelerate an important program."

On March 16, 2020 AcelRx Pharmaceuticals, Inc. (Nasdaq: ACRX), (AcelRx), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings, reported its fourth quarter and full year 2019 financial results (Press release, AcelRx Pharmaceuticals, MAR 16, 2020, View Source [SID1234555623]).

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"After only two quarters in 2019 with an expanded sales team, exceeding last year’s formulary and REMS objectives is a solid indicator of the growing acceptance of DSUVIA as a treatment option for the management of acute pain. We fully expect DSUVIA’s success to continue and look forward to the Department of Defense’s Milestone C meeting, which we believe will provide even more opportunities," continued Angotti. "I’m also excited about the announcement earlier today related to our acquisition of Tetraphase Pharmaceuticals, Inc., which will add a key, high growth product to the portfolio, enhancing our offering to healthcare institutions, while increasing the productivity of the commercial teams."

Fourth Quarter and Recent Highlights

Announced an agreement to acquire Tetraphase Pharmaceuticals in a stock for stock transaction at an exchange ratio of 0.6303 shares of AcelRx for each share of Tetraphase, valuing Tetraphase at $14.4 million as of the close of trading on March 13, 2020. Also entered into a co-promotion agreement to immediately begin realizing commercial combination benefits prior to closing of the acquisition.
The Company is on track to achieve its previously communicated target of 465 REMS-certified facilities and formulary approvals by the end of 2020. As of March 15, 2020, 218 healthcare facilities are now REMS-certified and able to purchase DSUVIA and 223 formulary approvals have been achieved.
Confirmed timing for April 2020 DSUVIA Milestone C meeting with the Department of Defense, with procurement recommendation expected post-meeting.
Announced an agreement with Brigham and Women’s Hospital for an investigator-initiated study led by Richard D. Urman MD, MBA, Associate Professor of Anesthesia and co-director of the Center for Perioperative Research at Brigham and Women’s Hospital and Harvard Medical School. The study plans to examine the perioperative use of DSUVIA in the analgesic regimen for spine surgery.
Financial Information

Cash, cash equivalents and short-term investments balance of $66.1 million as of December 31, 2019;
Fourth quarter 2019 net revenues were $0.5 million, and for the full year 2019 were $2.3 million, as previously announced;
Combined R&D and SG&A expenses for the fourth quarter of 2019 totaled $13.8 million compared to $10.4 million for the fourth quarter of 2018. Excluding stock-based compensation expense, these amounts were $12.6 million for the fourth quarter of 2019 compared to $9.2 million for the fourth quarter of 2018. R&D and SG&A expenses for the year ended December 31, 2019 totaled $49.7 million compared to $33.9 million for the year ended December 31, 2018. Excluding stock-based compensation expense, these figures were $44.9 million for the year ended December 31, 2019 compared to $29.1 million for the year ended December 31, 2018. The increase in combined R&D and SG&A expenses is primarily due to increased personnel-related expenses for the commercial launch of DSUVIA. See the "Reconciliation of Non-GAAP Financial Measures" table below for a reconciliation of the non-GAAP operating expenses described above to their related GAAP measures;
Net cash outflow for the fourth quarter of 2019 was $14.3 million, including $0.6 million in debt service, and for the year-ended December 31, 2019 was $39.6 million, and;
For the fourth quarter of 2019, net loss was $14.4 million, or $0.18 per basic and diluted share, compared to $12.6 million, or $0.18 per basic and diluted share, for the fourth quarter of 2018. Net loss for the year ended December 31, 2019 was $53.2 million, or $0.67 per basic and diluted share, compared to $47.1 million, or $0.81 per basic and diluted share, for the year ended December 31, 2018.
2020 Guidance
As previously announced, the Company’s year-end goals include obtaining 465 REMS-certified facilities and 465 formulary approvals in 2020. Quarterly combined R&D and SG&A expense in 2020 is expected to range from $10 million to $13 million, depending on the quarter, and includes approximately $1 million of non-cash stock-based compensation per quarter ($9 million to $12 million excluding stock-based compensation expense). Annual debt service is expected to approximate $6 million. Annual capital expenditures are expected to range from $4-$5 million attributed mainly to the installation of a new high-volume, automated packaging line at our contract manufacturer. These amounts do not consider the impact from the previously announced acquisition of Tetraphase Pharmaceuticals but reflect the benefits of the co-promotion agreement.

2020 financial guidance is based on the Company’s current expectations and are forward-looking statements. Actual results could differ materially depending on market conditions and the factors set forth under the "Forward-Looking Statements" heading below.

Webcast and Conference Call Information
As previously announced, AcelRx will host a live webcast Monday, March 16, 2020 at 8:30 a.m. Eastern Time (5:30 a.m. Pacific Time) to discuss these financial results and provide other corporate updates. The webcast is accessible by visiting the Investors page of the Company’s website at www.acelrx.com and clicking on the webcast link. The webcast will be accompanied by a slide presentation. Investors who wish to participate in the conference call may do so by dialing (866) 361-2335 for domestic callers, (855) 669-9657 for Canadian callers or (412) 902-4204 for international callers. A webcast replay will be available on the AcelRx website for 90 days following the call by visiting the Investor page of the Company’s website at www.acelrx.com.

About DSUVIA (sufentanil sublingual tablet), 30 mcg
DSUVIA, known as DZUVEO in Europe, approved by the FDA in November 2018, is indicated for use in adults in certified medically supervised healthcare settings, such as hospitals, surgical centers, and emergency departments, for the management of acute pain severe enough to require an opioid analgesic, and for which alternative treatments are inadequate. DSUVIA was designed to provide rapid analgesia via a non-invasive route and to eliminate dosing errors associated with intravenous (IV) administration. DSUVIA is a single-strength solid dosage form administered sublingually via a single-dose applicator (SDA) by healthcare professionals. Sufentanil is an opioid analgesic previously only marketed for IV and epidural anesthesia and analgesia. The sufentanil pharmacokinetic profile when delivered sublingually avoids the high peak plasma levels and short duration of action observed with IV administration. The European Commission approved DZUVEO for marketing in Europe in June 2018 and the Company is currently in discussions with potential European marketing partners.