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Portola Pharmaceuticals Receives FDA Orphan Drug Designation for Cerdulatinib, an Oral Syk/JAK Inhibitor for the Treatment of Peripheral T-Cell Lymphoma

On September 25, 2018 Portola Pharmaceuticals (Nasdaq: PTLA) reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to cerdulatinib, an investigational, oral Syk/JAK inhibitor for the treatment of peripheral T-cell lymphoma (PTCL) (Press release, Portola Pharmaceuticals, SEP 25, 2018, View Source;p=RssLanding&cat=news&id=2368929 [SID1234529770]).

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"We are pleased that the FDA has granted cerdulatinib Orphan Drug Designation, as it recognizes its potential to provide a significant clinical benefit to a group of patients with limited treatment options," said John Curnutte, M.D., Ph.D., Portola’s interim co-president and head of research and development. "We look forward to presenting additional data from the Phase 2a trial at a scientific congress early next year and to continuing discussions with the FDA regarding next steps for the development of cerdulatinib, including the potential for an accelerated approval pathway."

The FDA’s Office of Orphan Products Development grants orphan status to support development of medicines for the treatment of rare diseases that affect fewer than 200,000 people in the United States. Orphan Drug Designation may provide certain benefits, including a seven-year period of market exclusivity if the drug is approved, tax credits for qualified clinical trials and an exemption from FDA market application fees.

About PTCL
PTCL is a group of rare and often fast-growing lymphomas classified as a subtype of non-Hodgkin’s lymphoma. There are approximately 6,000 to 10,000 cases of PTCL annually in the United States. The three most common types of PTCL are anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), and PTCL not otherwise specified (PTCL-NOS), but many other rarer types exist. PTCL is most often treated with a combination of chemotherapies and the options for patients that fail front-line therapy are limited.

About Cerdulatinib
Cerdulatinib is an investigational oral, dual spleen tyrosine kinase (Syk) and janus kinase (JAK) inhibitor that uniquely inhibits two key cell signaling pathways implicated in certain hematologic malignancies and autoimmune diseases. There is a strong rationale for inhibiting both Syk (B-cell receptor pathway) and JAK (cytokine receptors) in B-cell malignancies where both targets have been shown to promote cancer cell growth and survival. In addition, pre-clinical data suggest an important role for Syk and JAK in peripheral T-cell lymphoma (PTCL) tumor survival.

In addition to PTCL, cerdulatinib is being evaluated in an ongoing Phase 2a study among patients with other specific subtypes of B-cell and T-cell Non-Hodgkin Lymphoma (NHL), including relapsed/refractory follicular lymphoma (FL) and chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL). The Company reported new data from this study in June at both the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper). Cerdulatinib demonstrated broad clinical activity including an objective response rate of 47 percent in all patients, and was generally well tolerated. Additionally, seven of the 20 patients in the PTCL cohort achieved a complete response at the time of presentation.

Checkpoint Therapeutics Announces Presentation of Updated Data from Phase 1/2 Trial of EGFR Inhibitor CK-101

On September 25, 2018 Checkpoint Therapeutics, Inc. ("Checkpoint") (NASDAQ: CKPT), a clinical-stage immuno-oncology biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for patients with solid tumor cancers, reported that positive preliminary safety and efficacy data from an ongoing Phase 1/2 clinical trial of CK-101 were presented yesterday in an oral presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer in Toronto (Press release, Checkpoint Therapeutics, SEP 25, 2018, View Source [SID1234529735]). The oral presentation included further details on, and updates from, the dataset announced previously. CK-101 is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) being evaluated in advanced non-small cell lung cancer (NSCLC).

"The oral presentation included exciting updates to the data released in the abstract, including intracranial disease responses to treatment with CK-101 in patients with brain metastases present at baseline indicating that CK-101 may cross the blood-brain barrier to reach metastases in the central nervous system, as well as an additional partial response post-data cutoff in a T790M mutation-positive NSCLC patient that failed previous TKI therapy," said James F. Oliviero, President and Chief Executive Officer of Checkpoint Therapeutics. "Based on these data, we believe CK-101 has the potential to be an effective and differentiated treatment option in a potential $6 billion market currently dominated by one approved therapy."

Highlights from the Oral Presentation
• CK-101 was well-tolerated across multiple dose groups
– Most adverse events were Grade 1-2
– Maximum-tolerated dose was not defined; no reported dose-limiting toxicities or treatmentrelated
serious adverse events
– No events of interstitial lung disease, pneumonitis, QTc prolongation, cardiomyopathy, nail
toxicities, stomatitis or hyperglycemia, which are notable observed side effects of marketed
TKI therapies
• CK-101 demonstrates preliminary activity in EGFR mutation-positive NSCLC
– 75% (6 of 8) objective response rate (ORR) in treatment-naïve patients
– 100% (19 of 19) disease control rate (DCR), including 84% (16 of 19) of patients with target
lesion reductions versus baseline
– 60% (3 of 5) of patients with baseline brain metastases had intracranial disease response
• Enrollment in the trial is ongoing to identify the optimal dose to maximize therapeutic effect,
following which a Phase 3 trial is planned to initiate in 2019 in treatment-naïve EGFR mutationpositive
NSCLC patients.

The first-in-human, multicenter trial is evaluating CK-101 in NSCLC patients with EGFR mutations and other advanced malignancies (NCT02926768). Following dose escalation ranging from 100 mg to 1,200 mg/day in patients with any solid tumor where targeted EGFR was deemed reasonable, a first doseexpansion cohort was enrolled at 400 mg twice daily in patients with a confirmed diagnosis of either (1) EGFR mutation-positive advanced or metastatic NSCLC without prior exposure to EGFR-TKI therapy, or (2) T790M-positive advanced or metastatic NSCLC with disease progression on previous EGFR-TKI therapy. There was no limit on the number of prior lines of systemic therapy patients received prior to entering the trial.

A copy of the oral presentation slides is available on the Publications page in the Pipeline section of
Checkpoint’s website, www.checkpointtx.com.

About CK-101
CK-101 (also known as RX518) is an oral, third-generation, irreversible kinase inhibitor against selective mutations in the EGFR gene. Activating mutations in the tyrosine kinase domain of EGFR, such as L858R and exon 19 deletion, are found in approximately 20 percent of patients with advanced non-small cell lung cancer (NSCLC).

Compared to chemotherapy, first-generation EGFR inhibitors significantly improved objective response rate and progression-free survival in previously untreated NSCLC patients carrying EGFR mutations. However, tumor progression could develop due to resistance mutations, often within months of treatment with first-generation EGFR inhibitors. The EGFR T790M "gatekeeper" mutation is the most common resistance mutation found in patients treated with first-generation EGFR inhibitors. The mutation decreases the affinity of first-generation inhibitors to EGFR kinase domain, rendering the drugs ineffective. Second-generation EGFR inhibitors have improved potency against the T790M mutation, but have not provided meaningful benefits in NSCLC patients due to toxicity from also inhibiting wild-type EGFR. Third-generation EGFR inhibitors are designed to be highly selective against both EGFR-TKIsensitizing and resistance mutations, with minimal activity on wild-type EGFR, thereby improving tolerability and safety profiles.

Checkpoint Therapeutics is developing CK-101 for the treatment of NSCLC patients carrying the susceptible EGFR mutations. These include the EGFR T790M mutation in second-line NSCLC patients, as well as the EGFR L858R and exon 19 deletion mutations in first-line NSCLC patients. Checkpoint holds an exclusive worldwide license (except with respect to certain Asian countries) to CK‐101, which it acquired from NeuPharma, Inc., in 2015.

BeiGene to Present at Upcoming Investor Conferences

On September 25, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that the company will present at two upcoming investor conferences (Press release, BeiGene, SEP 25, 2018, View Sourcephoenix.zhtml?c=254246&" target="_blank" title="View Sourcephoenix.zhtml?c=254246&" rel="nofollow">View Source;p=RssLanding&cat=news&id=2368716 [SID1234529678]):

The Ladenburg Thalmann 2018 Healthcare Conference in New York City on Tuesday, October 2, at 1 p.m. (ET); and

The Leerink Partners Roundtable Series: Rare Disease & Immuno-Oncology in New York City on Wednesday, October 3 at 3 p.m. (ET).
Live webcasts can be accessed from the investors section of BeiGene’s website at View Source and archived replays will be available for 90 days following each event.

Leap Therapeutics to Present at Two October Conferences

On September 25, 2018 Leap Therapeutics, Inc. (NASDAQ: LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, reported that Christopher K. Mirabelli, Ph.D., Chairman, President and Chief Executive Officer, will present a corporate overview at the following investor conferences (Press release, Leap Therapeutics, SEP 25, 2018, View Source;p=RssLanding&cat=news&id=2368738 [SID1234529666]):

The Ladenburg Thalmann 2018 Healthcare Conference in New York City on Tuesday, October 2, 2018 at 11:00 a.m. ET.
The Cantor Fitzgerald 2018 Global Healthcare Conference in New York City on Wednesday, October 3, 2018 at 8:00 a.m. ET.
These presentations will be webcast live and may be accessed on the Investors page of the company’s website at www.investors.leaptx.com, where a replay of the event will also be available for a limited time.

Roche’s Tecentriq in combination with chemotherapy helped people live significantly longer as an initial treatment for people with extensive-stage small cell lung cancer

On September 25, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive results from the Phase III IMpower133 study of Tecentriq (atezolizumab) plus carboplatin and etoposide (chemotherapy) for the initial (first-line) treatment of people with previously-untreated extensive-stage small cell lung cancer (ES-SCLC) (Press release, Hoffmann-La Roche, SEP 25, 2018, View Source [SID1234529660]). The analysis showed that Tecentriq and chemotherapy helped people live significantly longer compared with chemotherapy alone (overall survival [OS]=12.3 versus 10.3 months; hazard ratio [HR]=0.70, 95% CI: 0.54-0.91; p=0.0069) in the intention-to-treat (ITT) population.1 The Tecentriq -based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared with chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77, 95% CI: 0.62-0.96; p=0.017).1 Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

"The results with this Tecentriq combination in the initial treatment of extensive-stage small cell lung cancer represent the first clinically meaningful advance in the disease in over 20 years," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Our goal is to find treatment options for all types of lung cancer, and we are eager to work with global health authorities to bring this Tecentriq regimen to people living with this particularly difficult-to-treat form of lung cancer as soon as possible."

The data will be presented at the International Association for the Study of Lung Cancer (IASLC) 2018 World Conference on Lung Cancer (WCLC) Presidential Symposium on Tuesday, September 25, 2018, 9:00 – 9:15 a.m. EDT (Abstracts PL02.07 Oral). The data will be simultaneously published in the New England Journal of Medicine, and will be featured in the WCLC press conference at 09:45-10:30 a.m. EDT.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) versus chemotherapy (carboplatin plus etoposide) alone in chemotherapy-naïve people with ES-SCLC.

The study enrolled 403 people who were randomised equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the ITT population
OS in the ITT population
IMpower133 met its OS and PFS co-primary endpoints as per the study protocol. A summary of the results is included below:

Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. Grade 3-4 treatment-related adverse events (AEs) were reported in 56.6 percent of people receiving Tecentriq plus chemotherapy compared to 56.1 percent of people receiving chemotherapy alone.

About SCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.2 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and SCLC, with SCLC accounting for approximately 15% of all lung cancer cases.3 Survival rates for people with SCLC vary depending on the stage (extent) of the cancer at the time of diagnosis.4 The five-year relative survival rate for people with stage I SCLC is approximately 31%; however, at stage IV, the five-year relative survival rate declines to approximately 2%.5

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).