On August 7, 2019 AstraZeneca and Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported positive results from the Phase 3 PROfound trial of LYNPARZA in men with metastatic castration-resistant prostate cancer (mCRPC) who have an homologous recombination repair gene mutation (HRRm) and have progressed on prior treatment with new hormonal anticancer treatments (e.g. enzalutamide and abiraterone) (Press release, Merck & Co, AUG 7, 2019, View Source [SID1234538307]).

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Results from the trial showed a statistically-significant and clinically-meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS) with LYNPARZA vs. enzalutamide or abiraterone in men with mCRPC selected for BRCA 1/2 or ATM gene mutations, a subpopulation of HRR gene mutations. HRR gene mutations occur in approximately 25% of men diagnosed with mCRPC within which BRCA 1/2 and ATM form the majority. The safety and tolerability profile of LYNPARZA was generally consistent with previous trials.

José Baselga, executive vice president, Oncology R&D, AstraZeneca, said, "For men with metastatic castration-resistant prostate cancer, the disease remains deadly, especially in those who have failed on a new hormonal anticancer treatment. This is the only positive Phase 3 trial of any PARP inhibitor in metastatic castration-resistant prostate cancer, where the need for new, effective therapies is high. The PROfound trial also demonstrates the potential value of genomic testing in this at-risk patient population. We look forward to discussing these results with global health authorities soon."

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, "Metastatic castration-resistant prostate cancer is a deadly disease and represents an area of critical unmet medical need. The Phase 3 PROfound trial is another example of Merck and AstraZeneca’s shared commitment to improving long-term outcomes for people living with cancer. These results represent the potential for a new, oral, and targeted treatment option for this patient population."

AstraZeneca and Merck plan to present the full data from the trial at a future medical meeting. The companies are also exploring additional trials in prostate cancer, including the ongoing Phase 3 PROpel trial, evaluating LYNPARZA as a first-line therapy in mCRPC, in combination with abiraterone.

About PROfound

PROfound is a prospective, multi-center, randomized, open-label, Phase 3 trial evaluating the efficacy and safety of LYNPARZA versus enzalutamide or abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior treatment with a new hormonal anticancer treatment and have a qualifying tumor mutation in one of 15 genes involved in the homologous recombination repair (HRR) pathway, among them BRCA 1/2 , ATM and CDK12.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

Females

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males

Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/ nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%), and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—gBRCAm, HER2-negative metastatic breast cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in >25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min) but patients should be monitored closely for toxicity. In patients with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer

For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients with gBRCAm advanced epithelial ovarian, fallopian tube or primary peritoneal cancer for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

Advanced gBRCAm ovarian cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm, HER2-negative metastatic breast cancer

In patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

About LYNPARZA (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Prostate cancer is the second-most common cancer in men, with an estimated 1.6 million new cases diagnosed worldwide in 2015 and is associated with a significant mortality rate. Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these will have metastases at the time of CRPC diagnosis. Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. Despite an increase in the number of available therapies for men with mCRPC, remains low.

About Homologous Recombination Repair (HRR) Mutations

Homologous recombination repair (HRR) plays a significant role in maintaining the genetic stability of cells and suppressing tumor growth by repairing damaged DNA. Mutations, or defects, in homologous recombination (HR) pathway genes – which include ataxia telangiectasia mutated (ATM) and BRCA1/2 genes – increase the risk for breast, ovarian, pancreatic, prostate and other cancers.

About the AstraZeneca and Merck Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On August 7, 2019 Rexahn Pharmaceuticals, Inc. (NasdaqCM: REXN), a clinical stage biopharmaceutical company developing innovative therapies to improve patient outcomes in cancers that are difficult to treat, reported financial results for the three and six months ended June 30, 2019 and provided an update on RX-3117 development (Press release, Rexahn, AUG 7, 2019, View Source [SID1234538306]).

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Recent Highlights and RX-3117 Development Updates:

Announced a collaboration and license agreement with BioSense Global LLC, a New Jersey- and Suzhou, China-based biopharmaceutical company, to advance the development and commercialization of RX-3117 for pancreatic and other cancers in Greater China. Under the agreement, Rexahn will receive an upfront payment, a portion of which has been paid, and will be eligible to receive up to $126 million in development and regulatory milestones and up to $100 million in commercial milestones for each product containing RX-3117, contingent on achieving commercial goals.

As of July 24, 2019, an overall response rate of 23% has been observed in 40 patients that have had at least one scan on treatment in the Phase 2a study of RX-3117 in combination with ABRAXANE (paclitaxel protein-bound particles for injectable suspension) in patients newly diagnosed with metastatic pancreatic cancer. The Company previously reported in January 2019 an overall response rate of 38% in the first 24 patients who had at least one scan on treatment. Preliminary and unaudited data indicates that the median progression free survival for patients in the study is approximately 5.4 months. Patients currently active in the study will continue to be treated and final data from the trial is expected to be available in 2020.

Transferred its stock exchange listing to the Nasdaq Capital Market from its previous listing on NYSE American.

Effected a 1-for-12 reverse stock split of outstanding shares on April 12, 2019.

As of August 7, 2019, had approximately $15.3 million in cash, cash equivalents, and marketable securities (unaudited). Rexahn expects that its cash, cash equivalents and marketable securities will be sufficient to fund the company’s currently expected cash flow requirements for its activities for at least the next 12 months.

"We are surprised and disappointed with the most recent preliminary data from the ongoing Phase 2a trial of RX-3117 in combination with ABRAXANE in first line metastatic pancreatic cancer patients," said Douglas J. Swirsky president and chief executive officer of Rexahn. "RX-3117 appears to be well tolerated and we are evaluating development options for RX-3117 in other indications, including through our collaboration with BioSense. In the near term, we are focused on supporting our collaborations with BioSense and Zhejiang Haichang Biotechnology Co., Ltd. as we evaluate the best path forward for our programs."

See the discussion below under Important Cautionary Statements regarding our cash balance and the other forward-looking statements in this release.

Q2 2019 Financial Results:

R&D Expenses: Research and development expenses were $1.6 million for the three months ended June 30, 2019, compared to $3.4 million for the three months ended June 30, 2018. Research and development expenses were $3.9 million for the six months ended June 30, 2019, compared to $7.5 million for the six months ended June 30, 2018. The decrease in research and development expenses is primarily attributable to decreases in drug manufacturing and clinical trial costs and a reduction in preclinical programs and headcount.

G&A Expenses: General and administrative expenses were $1.3 million for the three months ended June 30, 2019 compared to $1.6 million for the three months ended June 30, 2018. General and administrative expenses were $3.0 million for the six months ended June 30, 2019 compared to $3.4 million for the six months ended June 30, 2018. The decrease is primarily attributable to a decrease in personnel expenses, offset by increases in professional fees.

Net Loss: Rexahn’s loss from operations was $3.0 million and $5.0 million for the three months ended June 30, 2019 and 2018, respectively. Rexahn’s net loss was $2.5 million, or $0.61 per share, for the three months ended June 30, 2019, compared to a net loss of $3.8 million, or $1.45 per share, for the three months ended June 30, 2018. For the six-month period ended June 30, 2019, Rexahn’s net loss was $4.8 million, or $1.23 per share, compared to a net loss of $5.9 million, or $2.24 per share for the six months ended June 30, 2018. The net loss for the six months ended June 30, 2019 and 2018 includes unrealized gains on the fair value of warrants of $1.9 million and $4.5 million, respectively. The fair value adjustments are non-cash charges and are primarily a result of changes in stock price between reporting periods.

On August 7, 2019 Athenex, Inc. (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer, reported its financial results and business highlights for the second quarter of 2019 (Press release, Athenex, AUG 7, 2019, View Source [SID1234538305]).

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"Athenex has continued to execute successfully across all of our strategic objectives in our development programs as well as our commercial operations and readiness," stated Dr. Johnson Lau, Chief Executive Officer and Chairman of Athenex. "We are particularly excited about today’s announcement of success in our Phase III study of oral paclitaxel and encequidar in metastatic breast cancer. We believe the success of this program serves to derisk our technology platform and provides further validation as we continue advancing our other Orascovery candidates (including docetaxel, cabazitaxel, irinotecan, topotecan and eribulin) and combination therapies."

Mr. Jeffrey Yordon, Chief Operating Officer of Athenex, commented, "We have been building the commercial infrastructure in manufacturing (active pharmaceutical ingredient and dosage-form), logistics and marketing to support the potential launch of oral paclitaxel and encequidar, which, based on the Phase III results announced, we believe has significant potential. Athenex is in the process of transforming from a clinical stage company to a fully integrated, commercial organization focused on delivering innovative cancer treatments that can improve patient outcomes."

Second Quarter 2019 and Recent Business Highlights:

Clinical Programs:

Phase III study of oral paclitaxel and encequidar for metastatic breast cancer

Primary efficacy endpoint met in Phase III clinical trial of oral paclitaxel and encequidar (Oral Paclitaxel) versus IV paclitaxel in patients with metastatic breast cancer. Oral Paclitaxel showed a statistically significant improvement compared to IV paclitaxel with an ORR of 36% compared to 24% based on intention-to-treat analysis (p = 0.01). Oral Paclitaxel also showed statistically significant improvement compared to IV paclitaxel based on other analyses on populations excluding non-evaluable patients (which would give higher response rates), with p £ 0.01 in all analyses.

Results also showed that the proportion of confirmed responders with a duration of response more than 150 days was 2.5 times higher in Oral Paclitaxel versus IV paclitaxel.

There were strong trends in progression-free survival (p = 0.077) and overall survival (p = 0.11) favoring Oral Paclitaxel over IV paclitaxel.

Neuropathy was less frequent with Oral Paclitaxel compared to IV paclitaxel.

Plan to request a pre-NDA meeting as soon as possible and present data at a major upcoming scientific meeting.

Other

Reported promising clinical results from a clinical study of oral paclitaxel and encequidar in cutaneous angiosarcoma. Preliminary data show rapid, visible response to oral paclitaxel and encequidar monotherapy in the first seven subjects, including three complete responses.

Four posters featuring the Company’s products/technologies were presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Preliminary positive clinical activity signals observed in a cohort of patients with psoriasis treated with tirbanibulin ointment (formerly known as KX2-391) in a Phase I clinical trial.

The U.S. Food and Drug Administration (FDA) allowed the Company’s Investigational New Drug (IND) application for the clinical investigation of PT01 (Pegtomarginase) for the treatment of patients with advanced malignancies.

Corporate Announcements:

Launched new brand, Athenex Oncology, and corresponding website, AthenexOncology.com, during the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting.

Strategically expanded presence in Europe and Latin America to grow the Company’s global clinical research and development capacity and maximize the global potential of its pipeline.

Formed a subsidiary in the U.K. and established offices in Manchester.

Entered into a definitive agreement to acquire certain assets of CIDAL Limited, a contract research organization (CRO) with headquarters in Guatemala and operations in various countries in Latin America.

Voluntarily suspended production activities at its active pharmaceutical ingredient (API) plant in Chongqing (Taihao API plant). This decision was made based on discussions with the Department of Emergency Management of Chongqing (DEMC) related to concerns raised about the location of our plant. The DEMC has been evaluating the safety of all chemical and other plants in the region after recent accidents at other plants. In the meantime, the Company has been working on the build-out of the new API plant in Chongqing, and the plant is expected to commence operations in the first half of 2020.

Commercial Business:

Athenex Pharmaceutical Division (APD) currently markets a total of 30 products with 58 SKUs.

Athenex Pharma Solutions (APS) currently markets 5 products in total with 13 SKUs.

Goal is to launch 9-12 products in 2019.

Financial Results for the Quarter Ended June 30, 2019

Product sales for the three months ended June 30, 2019 were $22.0 million, compared with $11.5 million for the three months ended June 30, 2018, an increase of $10.6 million or 92%. This increase was primarily attributable to an increase in 503B revenue of $6.0 million, an increase in specialty product revenue of $4.6 million, and an increase in API sales of $0.6 million.

Cost of sales for the three months ended June 30, 2019 totaled $16.9 million, an increase of $7.5 million, or 79%, as compared to $9.4 million for the three months ended June 30, 2018. This was primarily due to an increase of $5.8 million in cost of sales from the sale of specialty products and $1.7 million from 503B and API products. Gross margin attributable to product sales increased from 17.7% in the three months ended June 30, 2018 to 23.1% in the three months ended June 30, 2019, primarily as a result of change in product mix.

Research and development expenses for the three months ended June 30, 2019 were $18.5 million as compared to $26.6 million for the three months ended June 30, 2018. This was primarily due to a decrease in licensing fees, as well as expenses in relation to clinical operations and product development. The decrease in these R&D expenses was offset primarily by an increase of $1.1 million of preclinical development costs related to the arginase and TCR-T platforms.

Selling, general and administrative expenses for the three months ended June 30, 2019 were $17.2 million as compared to $12.8 million for the three months ended June 30, 2018. This was primarily due to an increase of $3.7 million related to the costs of preparing to commercialize our proprietary drugs, if approved, and an increase of $1.3 million in general administrative expenses including legal fees and other professional service fees, offset by a decrease of $0.6 million in administrative related compensation expense.

Net loss attributable to Athenex for the three months ended June 30, 2019 was $32.0 million, or $0.44 per diluted share, compared to a net loss of $36.9 million, or $0.58 per diluted share, in the same period last year.

On May 7, 2019, the Company closed a private placement transaction in which it issued 10 million shares of common stock to three institutional investors (Perceptive Advisors, Avoro Capital Advisors (formerly known as venBio Select Advisor) and OrbiMed) at a purchase price of $10.00 per share, for net proceeds of approximately $99.9 million to Athenex.

The Company received a $20 million milestone payment from Almirall S.A. during the second quarter of 2019 in connection with the partnership on tirbanibulin and expects this payment to be recorded as revenue in the second half of 2019.

At June 30, 2019, the Company had cash, cash equivalents, restricted cash and short-term investments of $165.9 million, compared to $107.4 million at December 31, 2018. Based on the current operating plan, we expect that our cash, cash equivalents, restricted cash and short-term investments as of June 30, 2019, together with cash to be generated from our operating activities, will enable us to fund our operations into the third quarter in 2020.

Financial Results for the Six Months Ended June 30, 2019

Product sales reached $47.2 million for the six months ended June 30, 2019, compared with $24.1 million for the six months ended June 30, 2018, an increase of $23.1 million or 96%.

Total revenue for the six months ended June 30, 2019 was $47.5 million, a decrease of $1.9 million, or 4%, as compared to $49.4 million for the six months ended June 30, 2018. The decrease was primarily due to $25.0 million related to license milestone revenue earned in the

first quarter of 2018, and $1.1 million decrease in medical device product sales and contract manufacturing revenue, offset by a $24.3 million the increase in product sales, of which $10.9 million was from the sales of 503B products, $10.5 million was from sales of specialty products, and $2.8 million was from API.

Cost of sales for the six months ended June 30, 2019 totaled $36.8 million, an increase of $16.1 million, or 77%, as compared to $20.8 million for the six months ended June 30, 2018. This was primarily due to the increase of $12.0 million in cost of sales from the sale of specialty products and $4.1 million in cost of sales from 503B and API products. Gross margin attributable to product sales increased from 13.7% in the six months ended June 30, 2018 to 21.9% in the six months ended June 30, 2019, primarily as a result of change in product mix.

Research and development expenses for the six months ended June 30, 2019 were $43.0 million as compared to $47.9 million for the six months ended June 30, 2018. This was primarily due to a decrease in licensing fees, as well as expenses in relation to clinical operations and product development. The decrease in these R&D expenses was offset by an increase of $2.8 million of preclinical development costs related to the arginase and TCR-T platforms, and a $1.7 million increase of R&D related compensation.

Selling, general and administrative expenses for the six months ended June 30, 2019 were $32.4 million as compared to $25.9 million for the six months ended June 30, 2018. This was primarily due to an increase of $6.2 million related to the costs of preparing to commercialize our proprietary drugs, if approved, and an increase of $1.3 million of general administrative expenses including legal fees and other professional service fees, offset by a decrease of $1.3 million in administrative related compensation expense.

Net loss attributable to Athenex for the six months ended June 30, 2019 was $67.3 million, or $0.96 per diluted share, compared to a net loss of $44.2 million, or $0.71 per diluted share, in the same period last year.

Outlook and Upcoming Milestones:

Intend to submit results from Phase III clinical trial of oral paclitaxel and encequidar in metastatic breast cancer for presentation at a major upcoming scientific meeting and for peer review publication (Q4 2019 / H1 2020)

Expect to request a pre-NDA meeting as soon as possible for oral paclitaxel and encequidar in metastatic breast cancer (Q4 2019)

Expect to file an NDA for tirbanibulin ointment in actinic keratosis (Q1 2020)

Financial Guidance:

Athenex provides revenue guidance for product sales only. The Company is raising its product sales guidance for 2019 and is now forecasting that product sales this year will increase by between 30% and 35% year-over-year from $56.4 million in 2018 (versus previous guidance of 25% – 30% annual growth). This new revenue guidance has taken into account the court’s latest decision in the Vasopressin proceeding and the suspension of operations at our Taihao API plant. The revenue guidance excludes license and collaboration fees.

Conference Call and Webcast Information:

The Company will host a conference call and live audio webcast today, Wednesday, August 7, 2019, at 8:00am Eastern Time to discuss the financial results and provide a business update.

To participate in the call, dial 877-407-0784 (domestic) or 201-689-8560 (international) fifteen minutes before the conference call begins and reference the conference passcode 13691069. The live conference call and replay can be accessed via audio webcast at View Source and also on the Investor Relations section of the Company’s website, located at View Source

On August 7, 2019 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers for patient enrichment, reported financial results for the second quarter ended June 30, 2019 and provided a corporate update (Press release, Jounce Therapeutics, AUG 7, 2019, View Source [SID1234538304]).

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"2019 has been a time of clinical progress and important strategic business development activity for Jounce, with the initiation of our Phase 2 EMERGE trial for vopratelimab, the completion of enrollment in our Phase 1 clinical trial of JTX-4014 and the recently announced renegotiation of our Celgene collaboration. These important developments demonstrate the value and utilization of our novel scientific platform and reverse translational analyses to further advance our immuno-oncology pipeline with an aim to match the right therapies to the right patients," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "Our translational science platform has been further validated by the establishment of our new licensing agreement with Celgene for the worldwide rights to JTX-8064. Now that we have retained full worldwide rights to vopratelimab, JTX-4014 and all of our discovery programs, we look forward to advancing our broad pipeline of potential next-generation immuno-oncology therapies."

Wholly-owned Programs:
Vopratelimab (JTX-2011)

Initiated Phase 2 EMERGE trial: In June 2019, Jounce announced the initiation of dosing in the Phase 2 EMERGE clinical trial of its lead product candidate, vopratelimab, in combination with ipilimumab in patients with non-small cell lung cancer or urothelial cancer who have progressed on or after PD-1/PD-L1 inhibitor therapies.

The primary endpoint of EMERGE is overall response rate and secondary endpoints include safety, duration of response, progression free survival (PFS) and overall survival (OS). Additional important assessments will include close monitoring of ICOS hi CD4 T cell emergence, and a range of other biomarkers, including exploratory assessment of potential predictive biomarkers. Jounce expects to report preliminary efficacy and biomarker relationships to clinical outcomes for up to 80 patients in 2020.

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

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

The characteristics of ICOS hi CD4 T cells associated with vopratelimab treatment via translational analyses demonstrated that vopratelimab stimulates only primed CD4 T cells with high levels of ICOS. The translational data shows that vopratelimab, unlike PD-1 inhibitors, leads to expansion and activation of peripheral CD4 T effector cells, and that these are observed in patients with clinical benefit.
JTX-4014

Completed enrollment of Phase 1 trial: Jounce is pleased to announce the completion of enrollment in the Phase 1 clinical trial of JTX-4014, its PD-1 inhibitor, and determination of the recommended Phase 2 dose. Jounce plans to report data from the trial in the second half of this year.
Discovery Pipeline

On track to announce next discovery candidate: Jounce continues to advance and develop its broad discovery pipeline, which includes multiple programs targeting T-regulatory cells, macrophages and stromal cells. Jounce expects to move its next novel program into IND-enabling studies later this year.
Licensed Program:

JTX-8064

Licensed JTX-8064: In July 2019, Jounce announced a new agreement in which Celgene exclusively licensed the worldwide rights to JTX-8064, a highly-selective, potential first-in-class antibody that targets the LILRB2 receptor on macrophages. Under this license agreement, Jounce received a $50.0 million non-refundable license fee and is eligible to receive up to $480.0 million in development, regulatory and commercial milestone payments, as well as potential royalties on worldwide sales. Celgene will be responsible for all development and commercialization of JTX-8064.

Jounce and Celgene also entered into a mutual agreement to terminate the original strategic collaboration agreement, established in July 2016. Jounce now retains full worldwide rights to its pipeline beyond JTX-8064, including vopratelimab, JTX-4014 and all discovery programs.
Second Quarter 2019 Financial Results:

Cash Position: As of June 30, 2019, cash, cash equivalents and investments were $152.0 million, compared to $195.9 million as of December 31, 2018. The decrease in cash, cash equivalents and investments was primarily due to operating costs incurred during the period. In July 2019, Jounce received a $50.0 million license fee pursuant to its new license agreement with Celgene.

Collaboration Revenue: Collaboration revenue was $17.4 million for the second quarter of 2019, compared to $19.4 million for the same period in 2018. Collaboration revenue during both periods represents non-cash revenue recognition relating to the $225.0 million upfront payment received in July 2016 upon the execution of Jounce’s original strategic collaboration with Celgene. In connection with the termination of the original strategic collaboration, Jounce expects that the remaining deferred revenue relating to the Celgene agreement will be fully recognized in the third quarter of 2019.

Research and Development Expenses: Research and development (R&D) expenses were $18.1 million for the second quarter of 2019, compared to $18.5 million for the same period in 2018. The decrease in R&D expenses was primarily due to $0.5 million of decreased external research and development costs attributable to vopratelimab manufacturing expenses incurred during the second quarter of 2018, $0.4 million of decreased external clinical and regulatory costs and $0.3 million of decreased lab consumables expenses. These decreases were partially offset by $0.7 million of increased employee compensation costs.

General and Administrative Expenses: General and administrative (G&A) expenses were $7.3 million for the second quarter of 2019, compared to $6.5 million for the same period in 2018. The increase in G&A expenses was primarily due to $0.5 million of increased employee compensation costs, including $0.3 million of increased stock-based compensation expense, and $0.3 million of increased other G&A costs to support Jounce’s operations.

Net Loss: Net loss was $7.0 million for the second quarter of 2019, or a basic and diluted net loss per share of $0.21. Net loss was $4.7 million for the same period in 2018, or a basic and diluted net loss per share of $0.14. The increase in net loss and net loss per share was primarily attributable to the decrease in non-cash collaboration revenue from the second quarter of 2018 to the second quarter of 2019.
Financial Guidance:

Jounce reiterates its updated revenue guidance and expects to record $50.0 million in cash revenue in 2019 related to the license of JTX-8064 and approximately $98.0 million in non-cash revenue in 2019 representing the remaining recognition of the Celgene upfront payment received in July 2016.

Based on its operating and development plans, Jounce continues to expect gross cash burn on operating expenses and capital expenditures for the full year 2019 to be approximately $80.0 million to $95.0 million.

Conference Call and Webcast Information:

Jounce Therapeutics will host a live conference call and webcast today at 8:00 a.m. ET. To access the conference call, please dial (866) 916-3380 (domestic) or (210) 874-7772 (international) and refer to conference ID 4484315. The live webcast can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days.

On August 7, 2019 INmune Bio, Inc. (NASDAQ: INMB), an immunology company focused on developing treatments that harness the patient’s innate immune system to fight disease, reported positive preliminary data today during a presentation at Cambridge Healthtech Institute’s 7th Annual Immuno-Oncology Summit in Boston (Press release, INmune Bio, AUG 7, 2019, View Source [SID1234538303]). INB03 is being developed as part of combination immunotherapy to potentially reverse resistance to treatment.

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The Phase I trial is an open-label, dose-escalation trial in patients with advanced solid tumors. Patients received INB03, a novel, second-generation soluble TNF (tumor necrosis factor) inhibitor that works by a dominant-negative technology. Today, positive preliminary data from the first two cohorts were released. These data will be followed by a final report later this year as the company advances the program into a Phase II study.

"The goal of the Phase I study is to determine, in order of priority, the safety of INB03 in cancer patients, the dose of INB03 to take into the Phase II trials in cancer, and evidence of a biologic effect of INB03," said RJ Tesi, MD, Chief Executive Officer and Chief Medical Officer of INmune Bio. "All of these goals have been met. Using data from this trial, we have begun planning a Phase II trial using INB03 as part of combination immunotherapy in patients with cancer."

To date, 11 of 12 patients have been enrolled in one of three dosing cohorts of INB03 (0.3, 1.0 and 3.0 mg/kg). Participants were a mix of patients with advanced solid tumors that have progressed after multiple previous lines of therapy. INB03 was given once a week by subcutaneous injection. Safety, INB03 pharmacokinetics and inflammatory biomarkers were followed in all patients.

Preliminary data from patients treated in the first two cohorts are available. Patients included two males and four females, and the average age was 63-years-old. Patients in the study had prostate cancer, ovarian cancer, colon cancer (two), cholangiocarcinoma and lung cancer, with an average of three previous lines of therapy (range: two to four). INB03 was given for a median of 74 days (range: 12 to 119 days). No drug-related serious adverse events have been reported, and INB03 was well tolerated. Discontinuation of INB03 was due to tumor progression in all patients. INB03 trough drug levels were obtained before each INB03 dose. The target INB03 trough level was reached in three of three patients in the 1.0 mg/kg group. The inflammatory cytokine IL6, a biomarker of soluble TNF function, decreased by more than 50% in half of the patients, suggesting a pharmacodynamic effect of INB03.

About INB03

INB03, a novel dominant-negative TNF inhibitor, is a selective second-generation TNF inhibitor that neutralizes soluble TNF (sTNF) without blocking the function of trans-membrane TNF or TNF receptors. In animal studies, INB03 neutralization of sTNF alters the immunobiology of the tumor microenvironment (TME) to improve tumor killing by decreasing populations of cells in the TME that protect the tumor from the patient’s immune system and immunotherapy – myeloid derived suppressor cells, T regulatory cells and tumor activated macrophages. The unique mechanism of action suggests INB03 may have safety and efficacy advantages over currently approved non-selective TNF inhibitors in the treatment of cancer and other diseases.