On November 14, 2019 KemPharm, Inc. (Nasdaq: KMPH), a specialty pharmaceutical company engaged in the discovery and development of proprietary prodrugs, reported its corporate and financial results for the quarter ended September 30, 2019 (Press release, KemPharm, NOV 14, 2019, View Source [SID1234551392]).

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"The third quarter of 2019 was highlighted by our entry into a licensing agreement (the KP415/KP484 Licensing Agreement) with an affiliate of Gurnet Point Capital (GPC) for our ADHD product candidates, KP415 and KP484," said Travis Mickle, Ph.D., President and Chief Executive Officer of KemPharm. "Working with the team that GPC has assembled, our immediate focus remains on finalizing the New Drug Application (NDA) for KP415, with the goal of filing in January 2020, or sooner if possible. However, the decision of when to file belongs to GPC."

Dr. Mickle continued, "Since our last announcement, KVK-Tech, Inc. (KVK-Tech) has informed us that APADAZ (benzhydrocodone and acetaminophen, or APAP, tablets) and its authorized generic, APADAZ-AG, are now available for wholesalers to place initial stocking orders. We look forward to further updates from our partner, KVK-Tech, as they begin their awareness efforts."

Q3 2019 Financial Results:
"Since the beginning of 2019, we have undertaken measures to reduce our operating spend, including a 33% workforce reduction, other general and administrative cost reductions, and the conclusion of the clinical phase for KP415. The KP415/KP484 License Agreement provides several milestone payments, including the $10M upfront payment we have already received, another milestone payable at acceptance of the KP415 NDA, potential regulatory milestones at approval and sales milestones post-approval. In addition, development cost reimbursements and consultation fee revenue for our support of all KP415 remaining development and commercial manufacturing provides the potential for us to cover a substantial portion of our operating expenses," said LaDuane Clifton, KemPharm’s Chief Financial Officer.

For Q3 2019, KemPharm reported revenue of $11.5 million, which included the $10 million upfront payment, development cost reimbursements and consultation fee revenue generated under the KP415/KP484 License Agreement. Net income for Q3 2019 was $3.1 million, or $0.09 per basic share and $0.06 per diluted share, compared to a net loss of $15.1 million, or $0.94 per basic and diluted share for Q3 2018. Net income for Q3 2019 was driven primarily by income from operations of $3.2 million and non-cash fair value adjustment income of $1.4 million which was offset by net interest expense and other expenses of approximately $1.5 million. Research and development expenses for Q3 2019 were $3.6 million, which was a reduction of 73% compared to $13.3 million in Q3 2018. General and administrative expenses for Q3 2019 were $3.6 million, which was an increase of $0.6 million compared to Q3 2018, primarily driven by an increase in professional fees incurred in connection with the KP415 licensing process and partially offset by a decrease in personnel costs.

As of September 30, 2019, total cash, which is comprised of cash, cash equivalents and restricted cash, was $7.0 million. Based on our current operating forecast, which includes principal and interest payments totaling approximately $9.2 million, which are due in the first half of 2020, currently available resources are sufficient to continue operations into but not through Q2 2020.

"We continue to explore additional options to reduce our near-term cash requirements, including pushing out the timing of upcoming near-term principal and interest payments with the goal of extending our cash runway past the potential approval of the KP415 NDA. In addition, we have initiated a process to explore addressing our debt in its entirety. For that purpose, we have engaged Cowen and Company, LLC, to serve as our financial advisors," Mr. Clifton concluded. While the Company is actively pursuing debt restructuring efforts, it cannot guarantee that those efforts will be successful for either the near- or long-term debt obligations.

The Company also reported that it expects to receive a notification from the Nasdaq Stock Market (Nasdaq) pertaining to its non-compliance with Nasdaq continued listing qualifications. Once received, the Company plans to submit a request to appear before the Nasdaq Hearings Panel and request an extension of the compliance period. Under Nasdaq rules, the Hearings Panel has the authority to extend the compliance period for up to an additional 180 days, subject to their review of the Company’s plan for regaining compliance with the continued listing requirements. During this process, KemPharm’s common stock would remain listed and active on the Nasdaq Global Market. There can be no assurance that the Company will be successful in maintaining the listing of its common stock on the Nasdaq Global Market.

Conference Call Information:

KemPharm will host a conference call and live audio webcast with slide presentation today, Thursday, November 14, 2019, at 5:30 p.m. ET, to discuss its corporate and financial results for the third quarter 2019. Interested participants and investors may access the conference call by dialing either:

(866) 395-2480 (U.S.)
(678) 509-7538 (international)
Conference ID: 8076615
An audio webcast with slide presentation will be accessible via the Investor Relations section of the KemPharm website View Source An archive of the webcast and presentation will remain available for 90 days beginning at approximately 6:30 p.m. ET, on November 14, 2019.

On November 14, 2019 The MISIS National Science and Technology Laboratory Biomedical Laboratory Science Team Conducted an Intravital (Live Tissue) Study of the Targeted Drug Delivery Mechanism based on liposomes for the treatment of malignant tumors (Press release, Misis university, NOV 14, 2019, View Source [SID1234551341]). It has been found that the immune cells of the body’s neutrophils increase the effectiveness of drug delivery for tumor treatment by 30%. The results have been published in the international scientific journal ACS Nano .

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Liposomes – artificially created adipose vesicles – penetrate the tumor due to the increased permeability and retention effect (in English EPR).

The EPR effect appears to be due to the excessive proliferation of blood vessels caused by an abnormal need for oxygen and tumor nutrition. As part of the pathological growth, huge pores up to 200 nm in diameter appear on the walls of blood vessels. In addition, the growth of the tumor causes compression of the lymphatic vessels and prevents the normal flow of intercellular fluid. Thus, liposomes penetrate the tumor and can not exit due to impaired lymphatic drainage.

It is assumed that because of the EPR effect, liposomes can only penetrate the tumor, not the healthy tissue. But is that true? And what’s going on inside the ship?

Scientists at the MISIS National University of Science and Technology’s biomedical nanomaterials laboratory investigated drug delivery in healthy mouse tissues and various types of malignancies: breast cancer, prostate cancer, and melanoma . Observations were made using an intravital microscope, which allows direct study of processes within a living organism.

"The first conclusion we drew from this study is that two types of liposome penetration from blood vessels to tissues occur within living tissues. A micro-leak is a small isolated accumulation of liposomes around a vessel. This process is useless for the treatment of tumors, as it does not allow the drug to reach the tumor cells. In addition, micro-leaks have been detected in healthy tissues, which explains the toxicity of liposome-based drugs used in a modern clinic. " , Said Viktor Naumenko , author of the work, researcher in the laboratory of biomedical nanomaterials National University of Science and Technology MISIS.

The second most interesting observation is that neutrophils, a type of white blood cell and an immune cell of the body, promote leakage to the tumor tissue. When the neutrophil leaves the vessel through the "door ajar" in the vascular wall, the liposomes manage to penetrate the tumor. According to the results obtained by the scientific team, neutrophils increase by a third the efficiency of the penetration of liposomes in the tumor.

This discovery reveals a clear pattern: neutrophils increase the vascular permeability of the tumor during the targeted administration of liposome-based drugs and therefore increase the chances of healing. In addition, this only occurs in the case of a micro-leak , a large, diffuse "cloud" of liposomes that penetrates deep into the tumor, and thus ensures targeted drug delivery.

"The distinction between two types of leaks is important for understanding the functioning of liposome drugs. Our results indicate not only that micro-leaks do not contribute to the penetration of drugs in tumor cells, but also that they are responsible for its undesirable accumulation in healthy tissues. The therapeutic effect is obtained thanks to the macro-leaks, and neutrophils can help strengthen it. " , Said Viktor Naumenko .

On November 14, 2019 Ascentage Pharma (6855.HK), a globally-focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, hepatitis B virus and age-related diseases, reported that the updated preliminary results from a Phase I clinical trial on the company’s novel investigational drug HQP1351 has been accepted for oral presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (Press release, Ascentage Pharma, NOV 14, 2019, View Source [SID1234551340]). Qian Jiang, M.D., who will be presenting, and Xiaojun Huang, M.D. from Peking University People’s Hospital, are the principal investigators of this study. HQP1351 is a third-generation BCR-ABL inhibitor for the treatment of drug-resistant chronic myeloid leukemia (CML).

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Early results from this Phase I study had been accepted for oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting in 2018. Being accepted for oral presentations two years in a row is a strong indication of the interest on HQP1351’s promising efficacy and safety data and updates.

The 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition will be held on December 7–10, 2019, in Orlando, Florida, United States. The ASH (Free ASH Whitepaper) Annual Meeting is the largest gathering of the international hematology field, bringing together the latest and most cutting-edge research and development in hematology.

The oral report will present updated safety and efficacy data from the Chinese Phase I trial of HQP1351. As of May 27, 2019, a total of 101 Chinese patients were enrolled in the study. Trial data have demonstrated that HQP1351 was well tolerated with good and durable anti-tumor activity in TKI-resistant CML patients, including those with the T315I mutation. HQP1351 is Ascentage Pharma’s novel investigational drug with the potential to effectively address the acquired drug resistance commonly associated with the first- and second-generation BCR-ABL inhibitors.

At ASH (Free ASH Whitepaper) 2019, in addition to the oral presentation on HQP1351, Ascentage Pharma will also release data in a poster presentation for a new research on the BCL-2/BCL-xL dual inhibitor APG-1252, which can overcome ibrutinib-resistance conferred by the upregulation of integrin pathway and BCL-xL. APG-1252 is one of the key drug candidates in Ascentage Pharma’s pipeline that focuses on restoring cell apoptosis function and inhibiting cancer growth.

Oral Presentation

Title: An Updated Safety and Efficacy Results of Phase 1 Study of HQP1351, a Novel Third Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia

Report#: 493
Session: 632
Presenter: Qian Jiang, MD
Time: Sunday, December 8, 4:30 pm (EST)
Location: W308, Orange County Convention Center (OCCC)

Poster Presentation

Title: A Novel BCL-2/BCL-xL Dual Inhibitor Overcomes Ibrutinib-Resistance Conferred By the Upregulation of Integrin Pathway and BCL-xL

Poster#: 2573
Session: 605
Time: Sunday, December 8, 6:00 PM – 8:00 PM (EST)
Location: Hall B, Orange County Convention Center (OCCC)

About HQP1351

HQP1351 is a novel kinase inhibitor developed by Ascentage Pharma. It is an oral third-generation BCR-ABL inhibitor targeting a broad spectrum of BCR-ABL mutants, including those with the T315I mutation, to treat drug-resistant CML patients. A Phase I clinical trial for patients with TKI-resistant CML has been completed and pivotal Phase II clinical trial are ongoing in China. In addition, a Phase I trial in patients with GIST has been initiated in China.

About APG-1252

APG-1252 is a novel, highly potent, small molecule drug designed to restore apoptosis through selective inhibition of the Bcl-2 and Bcl-xL proteins for the treatment of SCLC (small-cell lung cancer), lymphoma and other solid tumors. Ascentage is currently conducting two Phase I dose-escalation trials in patients with advanced cancers in the United States and Australia, and Phase I dose-escalation/expansion trial as a monotherapy in patients with SCLC in China.

On November 14, 2019 Bruker Corporation (Nasdaq: BRKR) reported that its Board of Directors has approved payment of a quarterly cash dividend in the amount of $0.04 per share on the Company’s common stock (Press release, Bruker, NOV 14, 2019, View Source [SID1234551339]). The dividend will be paid on December 20, 2019 to stockholders of record as of December 2, 2019.

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On November 14, 2019 Leap Therapeutics, Inc. (NASDAQ:LPTX) reported financial results for the third quarter ended September 30, 2019 (Press release, Leap Therapeutics, NOV 14, 2019, View Source [SID1234551338]).

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"The body of clinical data we presented in the third quarter for both DKN-01 monotherapy and combination treatment for cancer patients continues to demonstrate impressive activity. Patients with advanced gastroesophageal junction and gastric cancer whose tumors expressed high levels of DKK1 (DKK1-high) achieved higher survival and objective response outcomes to the combination of DKN-01 and KEYTRUDA," commented Christopher K. Mirabelli, Ph.D., President and Chief Executive Officer of Leap. "DKN-01 also showed durable benefit in patients with endometrial cancer with Wnt pathway alterations, including a monotherapy complete response, highlighting the potential utility of DKN-01 for biomarker-targeted patient populations."

Dr. Mirabelli continued: "We also completed enrollment in the dose escalation phase of our clinical trial evaluating TRX518 in combination with BAVENCIO and cyclophosphamide; however, we’ve made the strategic decision to deprioritize further development of TRX518 at this time in order to focus our resources on our more advanced DKN-01 program. The safety profile observed to date was acceptable, and patients who are benefiting from treatment in the TRX518 program will continue to be treated."

DKN-01 Development Program Update

DKN-01 in ESOPHAGOGASTRIC CANCER: Leap presented data from the KEYNOTE-731 clinical study evaluating DKN-01 in combination with KEYTRUDA (pembrolizumab) in patients with advanced esophagogastric cancer. Study results demonstrated that patients with DKK1-high status had improved outcomes, including longer progression free survival (PFS) independent of PD-L1 Combined Positive Scores (CPS). In ten evaluable gastroesophageal junction and gastric cancer patients who had not received prior PD-1/PD-L1 therapy, DKK1-high patients experienced 22.1 weeks median progression free survival (PFS) and 31.6 weeks median overall survival (OS), with a 50% overall response rate (ORR) and 80% disease control rate (DCR). Fifteen evaluable DKK1-low patients experienced 5.9 weeks PFS and 17.4 weeks OS, with a 20% DCR. PD-L1 CPS did not predict efficacy to the combination of DKN-01 plus KEYTRUDA.
DKN-01 in GYNECOLOGICAL CANCERS: The Company presented data from the ongoing clinical study of DKN-01 as a monotherapy and in combination with paclitaxel in patients with advanced gynecological cancers at the International Gynecologic Cancer Society Annual Global Meeting held in September. In the cohort of sixteen evaluable monotherapy patients with epithelial endometrial cancer (EEC) with identified Wnt signaling mutations, patients had higher response rates and demonstrated longer PFS as compared to patients without Wnt signaling mutations. Specifically, one patient had a complete response and one patient had a partial response, representing a 12.5% single agent ORR, seven patients had a best response of stable disease, and seven patients had progressive disease. In the six evaluable monotherapy EEC patients who did not have any identified Wnt signaling mutations, none had clinical benefit. Patient follow-up is continuing in this study, which has been expanded to include focused cohorts of patients with carcinosarcoma.
DKN-01 plus OPDIVO in BILIARY TRACT CANCER: The first patients have been dosed in an investigator-initiated clinical study to evaluate DKN-01 in combination with Bristol-Myers Squibb’s OPDIVO (nivolumab) in previously treated patients with advanced biliary tract cancer. The study is being conducted by Massachusetts General Hospital and will enroll up to 36 biliary tract cancer patients who have progressed after one or more lines of systemic therapy for advanced biliary tract cancer. The primary endpoint of the study will be ORR, to be assessed in the overall population as well as in subgroups stratified by tumor DKK1 and PD-L1 expression. Bristol-Myers Squibb is providing OPDIVO drug supply and partial funding for the study, with Leap providing DKN-01 drug supply as well as additional partial funding.
TRX518 Development Program Update

FURTHER DEVELOPMENT OF TRX518 HAS BEEN DEPRIORITIZED: Leap has completed enrollment in dose escalation phase of the clinical trial evaluating TRX518 in combination with cyclophosphamide chemotherapy and BAVENCIO (avelumab). However, instead of pursuing additional enrollment through the expansion cohorts in this study as initially planned, the Company has decided to reprioritize resources on the further development of the DKN-01 program. There were no safety or efficacy concerns leading to this decision, and patients who are benefitting from the combination therapy will continue to be treated in the study.
Selected Third Quarter 2019 Financial Results

Net loss was $7.9 million for the third quarter 2019, compared to $6.6 million for the same period in 2018. This increase was primarily due to the recording of a $1.8 million gain in the third quarter 2018 as a result of a change in the fair value of the warrant liability, partially offset by a decrease in research and development expense.

Research and development expenses were $5.8 million for the third quarter 2019, compared to $6.5 million for the same period in 2018. This decrease was primarily due to a decrease of $0.4 million in clinical trial costs as a result of the timing of patient enrollment and a decrease of $0.3 million in manufacturing costs related to clinical trial material manufacturing campaigns.

General and administrative expenses were $2.2 million for the third quarter 2019, compared to $2.1 million for the same period in 2018. The increase was primarily due to a $0.1 million increase in stock based compensation as a result of new stock options granted to employees and directors in 2019.

Cash, cash equivalents and marketable securities totaled $10.1 million at September 30, 2019. Research and development incentive receivables, short term, totaled approximately $752,000 at September 30, 2019.